...continued

<table><caption>Table S7: Baseline characteristics of the included participants, according to their higher hypertensive status. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure having hypertension). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No hypercholesterol</th><th>Hypercholesterol</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10"></td><td rowspan="10">Past tobacco smoking - visit 2, n (%)<br>Qualifications - visit 2, n (%)</td><td>Yes</td><td>644 (2.0)</td><td>490 (2.0)</td><td>154 (1.9)</td><td rowspan="10">&lt;0.001</td><td rowspan="10">Chi-squared</td><td rowspan="10">0.237</td></tr><tr><td>other</td><td>45 (0.1)</td><td>32 (0.1)</td><td>13 (0.2)</td></tr><tr><td>I have never smoked</td><td>15218 (46.8)</td><td>11865 (48.4)</td><td>3353 (42.1)</td></tr><tr><td>Just tried once or twice</td><td>5296 (16.3)</td><td>4185 (17.1)</td><td>1111 (14.0)</td></tr><tr><td>Smoked occasionally</td><td>4008 (12.3)</td><td>3080 (12.6)</td><td>928 (11.7)</td></tr><tr><td>Smoked on most or all days</td><td>7287 (22.4)</td><td>4904 (20.0)</td><td>2383 (29.9)</td></tr><tr><td>other</td><td>689 (2.1)</td><td>504 (2.1)</td><td>185 (2.3)</td></tr><tr><td>A levels/AS levels or equivalent</td><td>4013 (12.3)</td><td>3164 (12.9)</td><td>849 (10.7)</td></tr><tr><td>CSEs or equivalent</td><td>1205 (3.7)</td><td>905 (3.7)</td><td>300 (3.8)</td></tr><tr><td>College or University degree</td><td>16203 (49.9)</td><td>12636 (51.5)</td><td>3567 (44.8)</td></tr><tr><td>NVQ or HND or HNC or equivalent</td><td>1901 (5.8)</td><td>1280 (5.2)</td><td>621 (7.8)</td></tr><tr><td rowspan="3">Scanner lateral (x) brain position - visit 2, mean (SD)</td><td>None of the above</td><td>1762 (5.4)</td><td>1078 (4.4)</td><td>684 (8.6)</td></tr><tr><td>O levels/GCSEs or equivalent</td><td>5717 (17.6)</td><td>4274 (17.4)</td><td>1443 (18.1)</td></tr><tr><td>Other professional qualifications eg: nursing, teaching other</td><td>1596 (4.9)</td><td>1138 (4.6)</td><td>458 (5.8)</td></tr><tr><td rowspan="2">Scanner longitudinal (z) brain position - visit 2, mean (SD)</td><td>101 (0.3)</td><td>63 (0.3)</td><td>38 (0.5)</td></tr><tr><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.8 (3.0)</td></tr><tr><td rowspan="2">Scanner table position - visit 2, mean (SD)</td><td>-28.1 (26.8)</td><td>-27.2 (26.7)</td><td>-30.8 (26.7)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.049</td></tr><tr><td>-1054.2 (25.1)</td><td>-1054.4 (25.2)</td><td>-1053.8 (24.8)</td></tr><tr><td rowspan="2">Scanner transverse (y) brain position - visit 2, mean (SD)</td><td>66.4 (5.9)</td><td>66.1 (5.9)</td><td>67.1 (6.0)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.130</td></tr><tr><td>0.0 (0.2)</td><td>0.0 (0.1)</td><td>0.1 (0.2)</td></tr><tr><td rowspan="2">Self declared mental exclude visit 2, mean (SD)</td><td>17195 (52.9)</td><td>14342 (58.4)</td><td>2853 (35.8)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.465</td></tr><tr><td>15303 (47.1)</td><td>10196 (41.6)</td><td>5107 (64.2)</td></tr><tr><td rowspan="2">Sex - visit 0, n (%)</td><td>1065 (3.3)</td><td>808 (3.3)</td><td>257 (3.2)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.200</td></tr><tr><td>20503 (63.1)</td><td>16045 (65.4)</td><td>4458 (56.0)</td></tr><tr><td rowspan="2">Smoking status - visit 2, n (%)</td><td>10846 (33.4)</td><td>7630 (31.1)</td><td>3216 (40.4)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.054</td></tr><tr><td>84 (0.3)</td><td>55 (0.2)</td><td>29 (0.4)</td></tr><tr><td rowspan="2">Social support, n (%)</td><td>12720 (39.1)</td><td>9447 (38.5)</td><td>3273 (41.1)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.098</td></tr><tr><td>19778 (60.9)</td><td>15091 (61.5)</td><td>4687 (58.9)</td></tr><tr><td rowspan="2">Total alcohol weekly units 2, mean (SD)</td><td>13.1 (14.4)</td><td>12.8 (14.1)</td><td>14.2 (15.3)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.020</td></tr><tr><td>-1.9 (2.7)</td><td>-1.9 (2.7)</td><td>-1.9 (2.7)</td></tr><tr><td rowspan="2">Townsend deprivation index at recruitment - visit 0, mean (SD)</td><td>18991 (58.4)</td><td>14408 (58.7)</td><td>4583 (57.6)</td><td rowspan="2">0.068</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.035</td></tr><tr><td>8436 (26.0)</td><td>6299 (25.7)</td><td>2137 (26.8)</td></tr><tr><td rowspan="2">Uk biobank assessment centre - visit 2, n (%)</td><td>5028 (15.5)</td><td>3794 (15.5)</td><td>1234 (15.5)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.465</td></tr><tr><td>43 (0.1)</td><td>37 (0.2)</td><td>6 (0.1)</td></tr><tr><td rowspan="2">Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td>Cheadle</td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.213</td></tr><tr><td>Newcastle</td><td>-0.4 (10.5)</td><td>-1.8 (9.6)</td><td>3.6 (11.8)</td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No hypertension</th><th>Hypertension</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10">Sample size<br>Outcome<br>Mediators</td><td rowspan="10">n</td><td>G factor, mean (SD)</td><td>32498</td><td>23962</td><td>8536</td><td rowspan="10">&lt;0.001</td><td rowspan="10">Two Sample T-test</td><td>0.169</td></tr><tr><td>Dmri pc 0, mean (SD)</td><td>-0.0 (1.1)</td><td>-0.1 (1.1)</td><td>0.1 (1.2)</td><td>0.476</td></tr><tr><td>Dmri pc 1, mean (SD)</td><td>-0.3 (10.2)</td><td>-1.6 (9.3)</td><td>3.4 (11.5)</td><td>-0.225</td></tr><tr><td>Dmri pc 2, mean (SD)</td><td>0.1 (5.2)</td><td>0.4 (5.1)</td><td>-0.8 (5.5)</td><td>0.241</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td>-0.1 (5.0)</td><td>-0.4 (4.9)</td><td>0.8 (5.2)</td><td>0.226</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td>0.0 (4.4)</td><td>-0.3 (4.3)</td><td>0.7 (4.5)</td><td>-0.140</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td>0.0 (4.2)</td><td>0.2 (4.1)</td><td>-0.4 (4.7)</td><td>-0.061</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td>0.0 (3.4)</td><td>0.1 (3.3)</td><td>-0.2 (3.7)</td><td>0.497</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No hypertension</th><th>Hypertension</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="14">Confounders (alphabetic order)</td><td>Smri dmri pc 1, mean (SD)</td><td rowspan="14">No</td><td>-0.2 (7.4)</td><td>-0.1 (7.4)</td><td>-0.4 (7.5)</td><td>0.006</td><td>Two Sample T-test</td><td>-0.035</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td>0.1 (5.6)</td><td>0.5 (5.4)</td><td>-1.1 (5.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.284</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td>-0.0 (4.7)</td><td>-0.2 (4.6)</td><td>0.5 (4.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.150</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td>-0.0 (4.3)</td><td>-0.3 (4.3)</td><td>0.7 (4.4)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.223</td></tr><tr><td>Smri dmri pc 5, mean (SD)</td><td>0.0 (4.3)</td><td>0.2 (4.1)</td><td>-0.5 (4.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.170</td></tr><tr><td>Smri pc 0, mean (SD)</td><td>0.3 (7.2)</td><td>0.6 (7.1)</td><td>-0.7 (7.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.175</td></tr><tr><td>Smri pc 1, mean (SD)</td><td>-0.0 (3.3)</td><td>-0.3 (3.2)</td><td>0.8 (3.5)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.326</td></tr><tr><td>Smri pc 2, mean (SD)</td><td>-0.1 (2.8)</td><td>-0.4 (2.7)</td><td>0.8 (3.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.424</td></tr><tr><td>Smri pc 3, mean (SD)</td><td>0.0 (2.1)</td><td>-0.1 (2.0)</td><td>0.2 (2.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.146</td></tr><tr><td>Adopted as a child - visit 0, n (%)</td><td>32469 (99.9)</td><td>23939 (99.9)</td><td>8530 (99.9)</td><td>0.786</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.009</td></tr><tr><td>Age when attended assessment centre - visit 2, mean (SD)</td><td>Yes</td><td>9 (0.0)</td><td>7 (0.0)</td><td>2 (0.0)</td><td></td><td>Two Sample T-test</td><td>0.502</td></tr><tr><td>Alcohol above nhs reco, n (%)</td><td>other</td><td>20 (0.1)</td><td>16 (0.1)</td><td>4 (0.0)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.098</td></tr><tr><td rowspan="5">Alcohol intake frequency. - visit 2, n (%)</td><td>0</td><td>21256 (65.4)</td><td>15968 (66.6)</td><td>5288 (61.9)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.116</td></tr><tr><td>1</td><td>11242 (34.6)</td><td>7994 (33.4)</td><td>3248 (38.1)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.116</td></tr><tr><td>Daily or almost daily</td><td>5540 (17.0)</td><td>3890 (16.2)</td><td>1650 (19.3)</td><td></td><td></td><td></td></tr><tr><td>Never</td><td>2032 (6.3)</td><td>1464 (6.1)</td><td>568 (6.7)</td><td></td><td></td><td></td></tr><tr><td>Once or twice a week</td><td>8640 (26.6)</td><td>6611 (27.6)</td><td>2029 (23.8)</td><td></td><td></td><td></td></tr><tr><td rowspan="5">Average total household income before tax - visit 2, n (%)</td><td>One to three times a month</td><td>3788 (11.7)</td><td>2818 (11.8)</td><td>970 (11.4)</td><td></td><td>Chi-squared</td><td>0.188</td></tr><tr><td>Special occasions only</td><td>3262 (10.0)</td><td>2323 (9.7)</td><td>939 (11.0)</td><td></td><td></td><td></td></tr><tr><td>Three or four times a week</td><td>9236 (28.4)</td><td>6856 (28.6)</td><td>2380 (27.9)</td><td></td><td></td><td></td></tr><tr><td>18,000 to 30,999</td><td>7813 (24.0)</td><td>5488 (22.9)</td><td>2325 (27.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.188</td></tr><tr><td>31,000 to 51,999</td><td>9156 (28.2)</td><td>6707 (28.0)</td><td>2449 (28.7)</td><td></td><td></td><td></td></tr><tr><td rowspan="5">Body mass index (bmi) - visit 2, mean (SD)</td><td>52,000 to 100,000</td><td>7028 (21.6)</td><td>5495 (22.9)</td><td>1533 (18.0)</td><td></td><td></td><td></td></tr><tr><td>Do not know</td><td>961 (3.0)</td><td>693 (2.9)</td><td>268 (3.1)</td><td></td><td></td><td></td></tr><tr><td>Greater than 100,000</td><td>2277 (7.0)</td><td>1847 (7.7)</td><td>430 (5.0)</td><td></td><td></td><td></td></tr><tr><td>Less than 18,000</td><td>3402 (10.5)</td><td>2383 (9.9)</td><td>1019 (11.9)</td><td></td><td></td><td></td></tr><tr><td>Prefer not to answer</td><td>1861 (5.7)</td><td>1349 (5.6)</td><td>512 (6.0)</td><td></td><td></td><td></td></tr><tr><td>Breastfed as a baby - visit 0, n (%)</td><td>Do not know</td><td>6175 (19.0)</td><td>4231 (17.7)</td><td>28.0 (4.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.505</td></tr><tr><td rowspan="3">Cmdd final, n (%)</td><td>No</td><td>7174 (22.1)</td><td>5606 (23.4)</td><td>1568 (18.4)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.159</td></tr><tr><td>Yes</td><td>19136 (58.9)</td><td>14115 (58.9)</td><td>5021 (58.8)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>13 (0.0)</td><td>10 (0.0)</td><td>3 (0.0)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Comparative body size at age 10 - visit 0, n (%)</td><td>False</td><td>23413 (72.0)</td><td>17295 (72.2)</td><td>6118 (71.7)</td><td>0.381</td><td>Chi-squared</td><td>0.011</td></tr><tr><td>True</td><td>9085 (28.0)</td><td>6667 (27.8)</td><td>2418 (28.3)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.063</td></tr><tr><td rowspan="4">Comparative height size at age 10 - visit 0, n (%)</td><td>Do not know</td><td>347 (1.1)</td><td>239 (1.0)</td><td>108 (1.3)</td><td></td><td></td><td></td></tr><tr><td>Plumper</td><td>4922 (15.1)</td><td>3518 (14.7)</td><td>1404 (16.4)</td><td></td><td></td><td></td></tr><tr><td>Thinner</td><td>10584 (32.6)</td><td>7775 (32.4)</td><td>2809 (32.9)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.0)</td><td></td><td></td><td></td></tr><tr><td>Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>About average</td><td>17039 (52.4)</td><td>12478 (52.1)</td><td>4561 (53.4)</td><td>0.032</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.041</td></tr><tr><td rowspan="5">England</td><td>Do not know</td><td>293 (0.9)</td><td>201 (0.8)</td><td>92 (1.1)</td><td></td><td></td><td></td></tr><tr><td>Shorter</td><td>6569 (20.2)</td><td>4861 (20.3)</td><td>1708 (20.0)</td><td></td><td></td><td></td></tr><tr><td>Taller</td><td>8589 (26.4)</td><td>6416 (26.8)</td><td>2173 (25.5)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.0)</td><td></td><td></td><td></td></tr><tr><td>Elsewhere</td><td>1778 (5.5)</td><td>1331 (5.6)</td><td>447 (5.2)</td><td>0.559</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.028</td></tr><tr><td rowspan="5">Northern Ireland</td><td>England</td><td>27360 (84.2)</td><td>20162 (84.1)</td><td>7198 (84.3)</td><td></td><td></td><td></td></tr><tr><td>Shorter</td><td>234 (0.7)</td><td>179 (0.7)</td><td>55 (0.6)</td><td></td><td></td><td></td></tr><tr><td>Taller</td><td>217 (0.7)</td><td>162 (0.7)</td><td>55 (0.6)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>2296 (7.1)</td><td>1693 (7.1)</td><td>603 (7.1)</td><td></td><td></td><td></td></tr><tr><td>Elsewhere</td><td>600 (1.8)</td><td>425 (1.8)</td><td>175 (2.1)</td><td></td><td></td><td></td></tr><tr><td rowspan="5">Scotland</td><td>England</td><td>27360 (84.2)</td><td>20162 (84.1)</td><td>7198 (84.3)</td><td></td><td></td><td></td></tr><tr><td>Shorter</td><td>234 (0.7)</td><td>179 (0.7)</td><td>55 (0.6)</td><td></td><td></td><td></td></tr><tr><td>Taller</td><td>217 (0.7)</td><td>162 (0.7)</td><td>55 (0.6)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>2296 (7.1)</td><td>1693 (7.1)</td><td>603 (7.1)</td><td></td><td></td><td></td></tr><tr><td>Elsewhere</td><td>600 (1.8)</td><td>425 (1.8)</td><td>175 (2.1)</td><td></td><td></td><td></td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No hypertension</th><th>Hypertension</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="20"></td><td rowspan="20">Current employment status - visit 2, n (%)</td><td>other</td><td>13 (0.0)</td><td>10 (0.0)</td><td>3 (0.0)</td><td></td><td></td><td></td></tr><tr><td>In paid employment or self-employed</td><td>12978 (39.9)</td><td>10528 (43.9)</td><td>2450 (28.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.338</td></tr><tr><td>Retired</td><td>18302 (56.3)</td><td>12469 (52.0)</td><td>5833 (68.3)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>1218 (3.7)</td><td>965 (4.0)</td><td>253 (3.0)</td><td></td><td></td><td></td></tr><tr><td>0</td><td>31893 (98.1)</td><td>23497 (98.1)</td><td>8396 (98.4)</td><td>0.086</td><td>Chi-squared</td><td>0.023</td></tr><tr><td>1</td><td>605 (1.9)</td><td>465 (1.9)</td><td>140 (1.6)</td><td></td><td></td><td></td></tr><tr><td>Current smoker, n (%)</td><td>No</td><td>31431 (96.7)</td><td>23125 (96.5)</td><td>8306 (97.3)</td><td>0.001</td><td>Chi-squared</td><td>0.050</td></tr><tr><td>Current tobacco smoking - visit 2, n (%)</td><td>Yes, on most or all days</td><td>605 (1.9)</td><td>465 (1.9)</td><td>140 (1.6)</td><td></td><td></td><td></td></tr><tr><td>Diabetic, n (%)</td><td>other</td><td>462 (1.4)</td><td>372 (1.6)</td><td>90 (1.1)</td><td></td><td></td><td></td></tr><tr><td>0</td><td>31154 (95.9)</td><td>23462 (97.9)</td><td>7692 (90.1)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.333</td></tr><tr><td>1</td><td>1344 (4.1)</td><td>500 (2.1)</td><td>844 (9.9)</td><td></td><td></td><td></td></tr><tr><td>Ethnic background - visit 2, n (%)</td><td>British</td><td>7408 (22.8)</td><td>5305 (22.1)</td><td>2103 (24.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.059</td></tr><tr><td>Ever smoked - visit 2, n (%)</td><td>other</td><td>25090 (77.2)</td><td>18657 (77.9)</td><td>6433 (75.4)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Handedness (chirality/laterality) - visit 0, n (%)</td><td>No</td><td>15217 (46.8)</td><td>11408 (47.6)</td><td>3809 (44.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.060</td></tr><tr><td>Yes</td><td>17196 (52.9)</td><td>12495 (52.1)</td><td>4701 (55.1)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>85 (0.3)</td><td>59 (0.2)</td><td>26 (0.3)</td><td></td><td></td><td></td></tr><tr><td></td><td>Left-handed</td><td>3043 (9.4)</td><td>2242 (9.4)</td><td>801 (9.4)</td><td>0.406</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.021</td></tr><tr><td rowspan="20"></td><td rowspan="20">Hypercholesterol, n (%)</td><td>Right-handed</td><td>28957 (89.1)</td><td>21369 (89.2)</td><td>7588 (88.9)</td><td></td><td></td><td></td></tr><tr><td>Use both right and left hands equally</td><td>486 (1.5)</td><td>342 (1.4)</td><td>144 (1.7)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>12 (0.0)</td><td>9 (0.0)</td><td>3 (0.0)</td><td></td><td></td><td></td></tr><tr><td>0</td><td>24538 (75.5)</td><td>20377 (85.0)</td><td>4161 (48.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.836</td></tr><tr><td>1</td><td>7960 (24.5)</td><td>3585 (15.0)</td><td>4375 (51.3)</td><td></td><td></td><td></td></tr><tr><td>Inflammation, n (%)</td><td>False</td><td>27267 (83.9)</td><td>20553 (85.8)</td><td>6714 (78.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.187</td></tr><tr><td>True</td><td>5231 (16.1)</td><td>3409 (14.2)</td><td>1822 (21.3)</td><td></td><td></td><td></td></tr><tr><td>Job involves shift work - visit 2, n (%)</td><td>Always</td><td>795 (2.4)</td><td>644 (2.7)</td><td>151 (1.8)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.318</td></tr><tr><td>Never/rarely</td><td>11077 (34.1)</td><td>9008 (37.6)</td><td>2069 (24.2)</td><td></td><td></td><td></td></tr><tr><td>Sometimes</td><td>855 (2.6)</td><td>678 (2.8)</td><td>177 (2.1)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>19771 (60.8)</td><td>13632 (56.9)</td><td>6139 (71.9)</td><td></td><td></td><td></td></tr><tr><td>Length of time at current address - visit 2, mean (SD)</td><td>21.0 (13.9)</td><td>20.4 (13.5)</td><td>22.7 (14.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.166</td></tr><tr><td>Life long depression, n (%)</td><td>False</td><td>27461 (84.5)</td><td>20138 (84.0)</td><td>7323 (85.8)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.049</td></tr><tr><td></td><td>True</td><td>5037 (15.5)</td><td>3824 (16.0)</td><td>1213 (14.2)</td><td></td><td></td><td></td></tr><tr><td>Ls pc dim.1, mean (SD)</td><td></td><td>0.6 (2.0)</td><td>0.7 (2.0)</td><td>0.4 (2.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.169</td></tr><tr><td>Ls pc dim.2, mean (SD)</td><td></td><td>-0.4 (2.0)</td><td>-0.5 (2.0)</td><td>-0.4 (2.0)</td><td>0.009</td><td>Two Sample T-test</td><td>0.033</td></tr><tr><td>Maternal smoking around birth - visit 0, n (%)</td><td>Do not know</td><td>3388 (10.4)</td><td>2419 (10.1)</td><td>969 (11.4)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.072</td></tr><tr><td rowspan="10"></td><td rowspan="10">Mh pc dim.1, mean (SD)</td><td>No</td><td>20344 (62.6)</td><td>15217 (63.5)</td><td>5127 (60.1)</td><td></td><td></td><td></td></tr><tr><td>Yes</td><td>8749 (26.9)</td><td>6313 (26.3)</td><td>2436 (28.5)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>17 (0.1)</td><td>13 (0.1)</td><td>4 (0.0)</td><td></td><td></td><td></td></tr><tr><td>1.0 (6.5)</td><td>1.1 (6.5)</td><td>0.8 (6.7)</td><td>0.004</td><td>Two Sample T-test</td><td>-0.037</td></tr><tr><td>0.5 (3.3)</td><td>0.5 (3.3)</td><td>0.4 (3.3)</td><td>0.019</td><td>Two Sample T-test</td><td>-0.029</td></tr><tr><td>2.2 (1.0)</td><td>2.2 (1.1)</td><td>2.0 (0.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.161</td></tr><tr><td>1.0 (1.1)</td><td>1.1 (1.1)</td><td>1.0 (1.1)</td><td>0.011</td><td>Two Sample T-test</td><td>-0.032</td></tr><tr><td>Number of full brothers - visit 2, mean (SD)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Number of full sisters - visit 2, mean (SD)</td><td>Four or more</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>0.365</td><td>Two Sample T-test</td><td>-0.012</td></tr><tr><td>Number of vehicles in household - visit 2, n (%)</td><td></td><td>922 (2.8)</td><td>729 (3.0)</td><td>193 (2.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.118</td></tr><tr><td rowspan="10"></td><td rowspan="10">Obesity, n (%)</td><td>None</td><td>1265 (3.9)</td><td>902 (3.8)</td><td>363 (4.3)</td><td></td><td></td><td></td></tr><tr><td>One</td><td>13770 (42.4)</td><td>9885 (41.3)</td><td>3885 (45.5)</td><td></td><td></td><td></td></tr><tr><td>Three</td><td>3034 (9.3)</td><td>2380 (9.9)</td><td>654 (7.7)</td><td></td><td></td><td></td></tr><tr><td>Two</td><td>13471 (41.5)</td><td>10037 (41.9)</td><td>3434 (40.2)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>36 (0.1)</td><td>29 (0.1)</td><td>7 (0.1)</td><td></td><td></td><td></td></tr><tr><td>0</td><td>26781 (82.4)</td><td>20681 (86.3)</td><td>6100 (71.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.370</td></tr><tr><td>1</td><td>5717 (17.6)</td><td>3281 (13.7)</td><td>2436 (28.5)</td><td></td><td></td><td></td></tr><tr><td>Number of full sisters - visit 2, mean (SD)</td><td></td><td>31809 (97.9)</td><td>23448 (97.9)</td><td>8361 (97.9)</td><td>0.242</td><td>Chi-squared</td><td>0.021</td></tr><tr><td>Number of vehicles in household - visit 2, n (%)</td><td></td><td>644 (2.0)</td><td>485 (2.0)</td><td>159 (1.9)</td><td></td><td></td><td></td></tr><tr><td rowspan="2"></td><td rowspan="2">Part of a multiple birth - visit 0, n (%)</td><td>Yes</td><td>45 (0.1)</td><td>29 (0.1)</td><td>16 (0.2)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>15218 (46.8)</td><td>11409 (47.6)</td><td>3809 (44.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.181</td></tr><tr><td rowspan="2"></td><td rowspan="2">Past tobacco smoking - visit 2, n (%)</td><td>I have never smoked</td><td>5296 (16.3)</td><td>4118 (17.2)</td><td>1178 (13.8)</td><td></td><td></td><td></td></tr><tr><td>Just tried once or twice</td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>
...continued

<table><caption>Table S8: Baseline characteristics of for the included participants, according to their probable current major depressive disorder (cMMD) status. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure having a probable current major depressive disorder). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No hypertension</th><th>Hypertension</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="15">Qualifications - visit 2, n (%)</td><td rowspan="15">Smoked occasionally<br>Smoked on most or all days<br>other<br>A levels/AS levels or equivalent<br>CSEs or equivalent<br>College or University degree<br>NVQ or HND or HNC or equivalent<br>None of the above<br>O levels/GCSEs or equivalent<br>Other professional qualifications eg: nursing, teaching<br>other</td><td>4008 (12.3)</td><td>3001 (12.5)</td><td>1007 (11.8)</td><td></td><td></td><td></td></tr><tr><td>7287 (22.4)</td><td>4911 (20.5)</td><td>2376 (27.8)</td><td></td><td></td><td></td></tr><tr><td>689 (2.1)</td><td>523 (2.2)</td><td>166 (1.9)</td><td></td><td></td><td></td></tr><tr><td>4013 (12.3)</td><td>3024 (12.6)</td><td>989 (11.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.199</td></tr><tr><td>1205 (3.7)</td><td>901 (3.8)</td><td>304 (3.6)</td><td></td><td></td><td></td></tr><tr><td>16203 (49.9)</td><td>12376 (51.6)</td><td>3827 (44.8)</td><td></td><td></td><td></td></tr><tr><td>1901 (5.8)</td><td>1261 (5.3)</td><td>640 (7.5)</td><td></td><td></td><td></td></tr><tr><td>1762 (5.4)</td><td>1098 (4.6)</td><td>664 (7.8)</td><td></td><td></td><td></td></tr><tr><td>5717 (17.6)</td><td>4128 (17.2)</td><td>1589 (18.6)</td><td></td><td></td><td></td></tr><tr><td>1596 (4.9)</td><td>1111 (4.6)</td><td>485 (5.7)</td><td></td><td></td><td></td></tr><tr><td>101 (0.3)</td><td>63 (0.3)</td><td>38 (0.4)</td><td></td><td></td><td></td></tr><tr><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.8 (3.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.051</td></tr><tr><td>-28.1 (26.8)</td><td>-27.5 (26.4)</td><td>-29.8 (27.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.086</td></tr><tr><td>-1054.2 (25.1)</td><td>-1053.9 (24.8)</td><td>-1055.1 (26.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.045</td></tr><tr><td>66.4 (5.9)</td><td>66.2 (5.9)</td><td>66.9 (6.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.109</td></tr><tr><td>0.0 (0.2)</td><td>0.0 (0.1)</td><td>0.0 (0.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.120</td></tr><tr><td rowspan="2">Sex - visit 0, n (%)</td><td>Female</td><td>17195 (52.9)</td><td>13679 (57.1)</td><td>3516 (41.2)</td><td></td><td></td><td></td></tr><tr><td>Male</td><td>15303 (47.1)</td><td>10283 (42.9)</td><td>5020 (58.8)</td><td></td><td></td><td></td></tr><tr><td rowspan="4">Smoking status - visit 2, n (%)</td><td>Current</td><td>1065 (3.3)</td><td>835 (3.5)</td><td>230 (2.7)</td><td></td><td></td><td></td></tr><tr><td>Never</td><td>20503 (63.1)</td><td>15521 (64.8)</td><td>4982 (58.4)</td><td></td><td></td><td></td></tr><tr><td>Previous<br>other</td><td>10846 (33.4)</td><td>7548 (31.5)</td><td>3298 (38.6)</td><td></td><td></td><td></td></tr><tr><td>False</td><td>84 (0.3)</td><td>58 (0.2)</td><td>26 (0.3)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Social support, n (%)</td><td>False</td><td>12720 (39.1)</td><td>9175 (38.3)</td><td>3545 (41.5)</td><td></td><td></td><td></td></tr><tr><td>True</td><td>19778 (60.9)</td><td>14787 (61.7)</td><td>4991 (58.5)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Total alcohol weekly units 2, mean (SD)<br>Townsend deprivation index at recruitment - visit 0, mean (SD)</td><td></td><td>13.1 (14.4)</td><td>12.6 (13.6)</td><td>14.5 (16.4)</td><td></td><td></td><td></td></tr><tr><td></td><td>-1.9 (2.7)</td><td>-1.9 (2.7)</td><td>-1.9 (2.7)</td><td>0.435</td><td>Chi-squared</td><td>0.026</td></tr><tr><td rowspan="3">Uk biobank assessment centre - visit 2, n (%)</td><td>Cheadle</td><td>18991 (58.4)</td><td>13954 (58.2)</td><td>5037 (59.0)</td><td>0.241</td><td>Chi-squared</td><td>0.026</td></tr><tr><td>Newcastle</td><td>8436 (26.0)</td><td>6215 (25.9)</td><td>2221 (26.0)</td><td></td><td></td><td></td></tr><tr><td>Reading<br>other</td><td>5028 (15.5)</td><td>3763 (15.7)</td><td>1265 (14.8)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td></td><td>43 (0.1)</td><td>30 (0.1)</td><td>13 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.169</td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No cMMD</th><th>cMMD</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td>Sample size</td><td>n</td><td></td><td>32498</td><td>23413</td><td>9085</td><td></td><td></td><td></td></tr><tr><td rowspan="10">Outcome<br>Mediators</td><td>G factor, mean (SD)</td><td></td><td>-0.0 (1.1)</td><td>-0.0 (1.1)</td><td>-0.0 (1.1)</td><td>0.064</td><td>Two Sample T-test</td><td>0.023</td></tr><tr><td>Dmri pc 0, mean (SD)</td><td></td><td>-0.3 (10.2)</td><td>-0.0 (10.2)</td><td>-1.0 (10.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.096</td></tr><tr><td>Dmri pc 1, mean (SD)</td><td></td><td>0.1 (5.2)</td><td>-0.1 (5.2)</td><td>0.5 (5.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.118</td></tr><tr><td>Dmri pc 2, mean (SD)</td><td></td><td>-0.1 (5.0)</td><td>-0.1 (5.1)</td><td>-0.2 (4.9)</td><td>0.143</td><td>Two Sample T-test</td><td>-0.018</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td></td><td>0.0 (4.4)</td><td>0.0 (4.4)</td><td>-0.0 (4.3)</td><td>0.519</td><td>Two Sample T-test</td><td>-0.008</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td></td><td>0.0 (4.2)</td><td>-0.0 (4.2)</td><td>0.1 (4.3)</td><td>0.066</td><td>Two Sample T-test</td><td>0.023</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td></td><td>0.0 (3.4)</td><td>-0.0 (3.4)</td><td>0.1 (3.4)</td><td>0.015</td><td>Two Sample T-test</td><td>0.030</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td></td><td>-0.4 (10.5)</td><td>-0.1 (10.5)</td><td>-1.1 (10.4)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.093</td></tr><tr><td>Smri dmri pc 1, mean (SD)</td><td></td><td>-0.2 (7.4)</td><td>-0.3 (7.5)</td><td>0.2 (7.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.076</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td></td><td>0.1 (5.6)</td><td>-0.1 (5.6)</td><td>0.6 (5.4)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.115</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td></td><td>-0.0 (4.7)</td><td>-0.0 (4.7)</td><td>0.0 (4.7)</td><td>0.316</td><td>Two Sample T-test</td><td>0.012</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td></td><td>-0.0 (4.3)</td><td>-0.0 (4.3)</td><td>-0.1 (4.3)</td><td>0.404</td><td>Two Sample T-test</td><td>-0.010</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No cMMD</th><th>cMMD</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="15">Confounders (alphabetic order)</td><td>Smri dmri pc 5, mean (SD)</td><td rowspan="5">No</td><td>0.0 (4.3)</td><td>0.0 (4.3)</td><td>0.1 (4.3)</td><td>0.034</td><td>Two Sample T-test</td><td>0.026</td></tr><tr><td>Smri pc 0, mean (SD)</td><td>0.3 (7.2)</td><td>0.3 (7.2)</td><td>0.1 (7.1)</td><td>0.038</td><td>Two Sample T-test</td><td>-0.026</td></tr><tr><td>Smri pc 1, mean (SD)</td><td>-0.0 (3.3)</td><td>0.0 (3.3)</td><td>-0.3 (3.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.091</td></tr><tr><td>Smri pc 2, mean (SD)</td><td>-0.1 (2.8)</td><td>0.1 (2.8)</td><td>-0.4 (2.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.172</td></tr><tr><td>Smri pc 3, mean (SD)</td><td>0.0 (2.1)</td><td>0.0 (2.1)</td><td>0.0 (2.0)</td><td>0.920</td><td>Two Sample T-test</td><td>-0.001</td></tr><tr><td>Adopted as a child - visit 0, n (%)</td><td>32469 (99.9)</td><td>23391 (99.9)</td><td>9078 (99.9)</td><td>0.685</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.011</td></tr><tr><td>Age when attended assessment centre - visit 2, mean (SD)</td><td>Yes</td><td>9 (0.0)</td><td>6 (0.0)</td><td>3 (0.0)</td><td></td><td>Two Sample T-test</td><td>-0.288</td></tr><tr><td>Alcohol above nhs reco, n (%)</td><td>1</td><td>21256 (65.4)</td><td>15211 (65.0)</td><td>6045 (66.5)</td><td>0.008</td><td>Chi-squared</td><td>0.033</td></tr><tr><td>Alcohol intake frequency - visit 2, n (%)</td><td>Daily or almost daily</td><td>11242 (34.6)</td><td>8202 (35.0)</td><td>3040 (33.5)</td><td></td><td>Chi-squared</td><td>0.114</td></tr><tr><td rowspan="5">Average total household income before tax - visit 2, n (%)</td><td>Never</td><td>5540 (17.0)</td><td>3996 (17.1)</td><td>1544 (17.0)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.132</td></tr><tr><td>Once or twice a week</td><td>2032 (6.3)</td><td>1415 (6.0)</td><td>617 (6.8)</td><td></td><td>Chi-squared</td><td>0.132</td></tr><tr><td>One to three times a month</td><td>8640 (26.6)</td><td>6354 (27.1)</td><td>2286 (25.2)</td><td></td><td>Chi-squared</td><td>0.132</td></tr><tr><td>Special occasions only</td><td>3788 (11.7)</td><td>2609 (11.1)</td><td>1179 (13.0)</td><td></td><td>Chi-squared</td><td>0.132</td></tr><tr><td>Three or four times a week</td><td>3262 (10.0)</td><td>2200 (9.4)</td><td>1062 (11.7)</td><td></td><td>Chi-squared</td><td>0.132</td></tr><tr><td rowspan="6">Body mass index (bmi) - visit 2, mean (SD)</td><td>18,000 to 30,999</td><td>9156 (28.2)</td><td>6670 (28.5)</td><td>2486 (27.4)</td><td></td><td>Two Sample T-test</td><td>0.133</td></tr><tr><td>31,000 to 51,999</td><td>7028 (21.6)</td><td>5178 (22.1)</td><td>1850 (20.4)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.083</td></tr><tr><td>52,000 to 100,000</td><td>961 (3.0)</td><td>640 (2.7)</td><td>321 (3.5)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.125</td></tr><tr><td>Do not know</td><td>2277 (7.0)</td><td>1729 (7.4)</td><td>548 (6.0)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.048</td></tr><tr><td>Greater than 100,000</td><td>3402 (10.5)</td><td>2237 (9.6)</td><td>1165 (12.8)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.048</td></tr><tr><td>Less than 18,000</td><td>1861 (5.7)</td><td>1385 (5.9)</td><td>476 (5.2)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>Breastfed as a baby - visit 0, n (%)</td><td>Do not know</td><td>6175 (19.0)</td><td>4471 (19.1)</td><td>1704 (18.8)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.083</td></tr><tr><td rowspan="2">Comparative body size at age 10 - visit 0, n (%)</td><td>No</td><td>7174 (22.1)</td><td>4944 (21.1)</td><td>2230 (24.5)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.125</td></tr><tr><td>Yes</td><td>19136 (58.9)</td><td>13988 (59.7)</td><td>5148 (56.7)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.125</td></tr><tr><td>Comparative height size at age 10 - visit 0, n (%)</td><td>About average</td><td>13 (0.0)</td><td>10 (0.0)</td><td>3 (0.0)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.048</td></tr><tr><td rowspan="4">Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>Do not know</td><td>347 (1.1)</td><td>256 (1.1)</td><td>91 (1.0)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.048</td></tr><tr><td>Plumper</td><td>4922 (15.1)</td><td>3328 (14.2)</td><td>1594 (17.5)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.048</td></tr><tr><td>Thinner</td><td>10584 (32.6)</td><td>7462 (31.9)</td><td>3122 (34.4)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.048</td></tr><tr><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.0)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td rowspan="3">Current employment status - visit 2, n (%)</td><td>Do not know</td><td>293 (0.9)</td><td>210 (0.9)</td><td>83 (0.9)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>Shorter</td><td>6569 (20.2)</td><td>4626 (19.8)</td><td>1943 (21.4)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>Taller</td><td>8589 (26.4)</td><td>6152 (26.3)</td><td>2437 (26.8)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td rowspan="2">Current smoker, n (%)</td><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.0)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>In paid employment or self-employed</td><td>1778 (5.5)</td><td>1279 (5.5)</td><td>499 (5.5)</td><td>0.496</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td rowspan="4"></td><td>England</td><td>27360 (84.2)</td><td>19663 (84.0)</td><td>7697 (84.7)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>Northern Ireland</td><td>234 (0.7)</td><td>170 (0.7)</td><td>64 (0.7)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>Republic of Ireland</td><td>217 (0.7)</td><td>160 (0.7)</td><td>57 (0.6)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>Scotland</td><td>2296 (7.1)</td><td>1700 (7.3)</td><td>596 (6.6)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td rowspan="3"></td><td>Wales</td><td>600 (1.8)</td><td>432 (1.8)</td><td>168 (1.8)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>other</td><td>13 (0.0)</td><td>9 (0.0)</td><td>4 (0.0)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>In paid employment or self-employed</td><td>12978 (39.9)</td><td>8764 (37.4)</td><td>4214 (46.4)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td rowspan="3"></td><td>Retired</td><td>18302 (56.3)</td><td>13962 (59.6)</td><td>4340 (47.8)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>other</td><td>1218 (3.7)</td><td>687 (2.9)</td><td>531 (5.8)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr><tr><td>0</td><td>31893 (98.1)</td><td>23036 (98.4)</td><td>8857 (97.5)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.029</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No cMMD</th><th>cMMD</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="2">Current tobacco smoking - visit 2, n (%)</td><td>No</td><td>1</td><td>605 (1.9)</td><td>377 (1.6)</td><td>228 (2.5)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.072</td></tr><tr><td>Yes, on most or all days other</td><td>605 (1.9)</td><td>22729 (97.1)</td><td>8702 (95.8)</td><td>228 (2.5)</td></tr><tr><td rowspan="2">Diabetic, n (%)</td><td>0</td><td>462 (1.4)</td><td>377 (1.6)</td><td>307 (1.3)</td><td>155 (1.7)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.048</td></tr><tr><td>1</td><td>31154 (95.9)</td><td>22509 (96.1)</td><td>8645 (95.2)</td><td>440 (4.8)</td></tr><tr><td rowspan="2">Ethnic background - visit 2, n (%)</td><td>British</td><td>0</td><td>1344 (4.1)</td><td>904 (3.9)</td><td>2167 (23.9)</td><td rowspan="2">0.005</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.035</td></tr><tr><td>other</td><td>7408 (22.8)</td><td>5241 (22.4)</td><td>18172 (77.6)</td><td>6918 (76.1)</td></tr><tr><td rowspan="2">Ever smoked - visit 2, n (%)</td><td>No</td><td>15217 (46.8)</td><td>11344 (48.5)</td><td>3873 (42.6)</td><td>5187 (57.1)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.117</td></tr><tr><td>Yes</td><td>17196 (52.9)</td><td>12009 (51.3)</td><td>60 (0.3)</td><td>25 (0.3)</td></tr><tr><td rowspan="2">Handedness (chirality/laterality) - visit 0, n (%)</td><td>Left-handed</td><td>3043 (9.4)</td><td>2145 (9.2)</td><td>898 (9.9)</td><td>0.180</td><td rowspan="2">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="2">0.027</td></tr><tr><td>Right-handed</td><td>28957 (89.1)</td><td>20901 (89.3)</td><td>8056 (88.7)</td><td></td></tr><tr><td rowspan="2">Hypercholesterol, n (%)</td><td>Use both right and left hands equally</td><td>486 (1.5)</td><td>359 (1.5)</td><td>127 (1.4)</td><td></td><td rowspan="2">0.005</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.035</td></tr><tr><td>other</td><td>12 (0.0)</td><td>8 (0.0)</td><td>4 (0.0)</td><td></td></tr><tr><td rowspan="2">Hypertensive, n (%)</td><td>0</td><td>24538 (75.5)</td><td>17579 (75.1)</td><td>6959 (76.6)</td><td></td><td rowspan="2">0.381</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.011</td></tr><tr><td>1</td><td>7960 (24.5)</td><td>5834 (24.9)</td><td>2126 (23.4)</td><td></td></tr><tr><td rowspan="2">Inflammation, n (%)</td><td>0</td><td>23962 (73.7)</td><td>17295 (73.9)</td><td>6667 (73.4)</td><td></td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.048</td></tr><tr><td>1</td><td>8536 (26.3)</td><td>6118 (26.1)</td><td>2418 (26.6)</td><td></td></tr><tr><td rowspan="3">Job involves shift work - visit 2, n (%)</td><td>False</td><td>27267 (83.9)</td><td>19760 (84.4)</td><td>7507 (82.6)</td><td></td><td rowspan="3">&lt;0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.177</td></tr><tr><td>True</td><td>5231 (16.1)</td><td>3653 (15.6)</td><td>1578 (17.4)</td><td></td></tr><tr><td>Always</td><td>795 (2.4)</td><td>518 (2.2)</td><td>277 (3.0)</td><td></td></tr><tr><td rowspan="3">Length of time at current address - visit 2, mean (SD)</td><td>Never/rarely</td><td>11077 (34.1)</td><td>7539 (32.2)</td><td>3538 (38.9)</td><td></td><td rowspan="3">&lt;0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.177</td></tr><tr><td>Sometimes</td><td>855 (2.6)</td><td>552 (2.4)</td><td>303 (3.3)</td><td></td></tr><tr><td>other</td><td>19771 (60.8)</td><td>14804 (63.2)</td><td>4967 (54.7)</td><td></td></tr><tr><td>Life long depression, n (%)</td><td>False</td><td>27461 (84.5)</td><td>20823 (88.9)</td><td>19.4 (13.6)</td><td></td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.158</td></tr><tr><td>True</td><td>5037 (15.5)</td><td>2590 (11.1)</td><td>2447 (26.9)</td><td></td></tr><tr><td>Ls pc dim.1, mean (SD)</td><td></td><td>0.6 (2.0)</td><td>0.8 (2.0)</td><td>0.2 (2.2)</td><td></td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.413</td></tr><tr><td>Ls pc dim.2, mean (SD)</td><td></td><td>-0.4 (2.0)</td><td>-0.4 (2.0)</td><td>-0.6 (2.0)</td><td></td></tr><tr><td>Maternal smoking around birth - visit 0, n (%)</td><td>Do not know</td><td>3388 (10.4)</td><td>2453 (10.5)</td><td>935 (10.3)</td><td></td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="2">0.075</td></tr><tr><td>No</td><td>20344 (62.6)</td><td>14861 (63.5)</td><td>5483 (60.4)</td><td></td></tr><tr><td>Yes</td><td>8749 (26.9)</td><td>6087 (26.0)</td><td>2662 (29.3)</td><td></td><td rowspan="2">0.006</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.035</td></tr><tr><td>other</td><td>17 (0.1)</td><td>12 (0.1)</td><td>5 (0.1)</td><td></td></tr><tr><td>Number in household - visit 2, mean (SD)</td><td></td><td>2.2 (1.0)</td><td>2.1 (1.0)</td><td>2.2 (1.1)</td><td></td><td rowspan="2">0.074</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.022</td></tr><tr><td>Number of full brothers - visit 2, mean (SD)</td><td></td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.1 (1.1)</td><td></td></tr><tr><td>Number of full sisters - visit 2, mean (SD)</td><td></td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td></td><td rowspan="2">0.004</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.036</td></tr><tr><td>Number of vehicles in household - visit 2, n (%)</td><td>Four or more</td><td>922 (2.8)</td><td>648 (2.8)</td><td>274 (3.0)</td><td></td></tr><tr><td rowspan="2">Obesity, n (%)</td><td>None</td><td>1265 (3.9)</td><td>814 (3.5)</td><td>451 (5.0)</td><td></td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.135</td></tr><tr><td>One</td><td>13770 (42.4)</td><td>9829 (42.0)</td><td>3941 (43.4)</td><td></td></tr><tr><td rowspan="2">Part of a multiple birth - visit 0, n (%)</td><td>Three</td><td>3034 (9.3)</td><td>2198 (9.4)</td><td>836 (9.2)</td><td></td><td rowspan="2">0.089</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.025</td></tr><tr><td>Two</td><td>13471 (41.5)</td><td>9899 (42.3)</td><td>3572 (39.3)</td><td></td></tr><tr><td rowspan="2">Past tobacco smoking - visit 2, n (%)</td><td>other</td><td>36 (0.1)</td><td>25 (0.1)</td><td>11 (0.1)</td><td></td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.142</td></tr><tr><td>0</td><td>26781 (82.4)</td><td>19639 (83.9)</td><td>7142 (78.6)</td><td></td></tr><tr><td rowspan="3">Qualifications - visit 2, n (%)</td><td>1</td><td>5717 (17.6)</td><td>3774 (16.1)</td><td>1943 (21.4)</td><td></td><td rowspan="3">&lt;0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.098</td></tr><tr><td>No</td><td>31809 (97.9)</td><td>22917 (97.9)</td><td>8892 (97.9)</td><td></td></tr><tr><td>Yes</td><td>644 (2.0)</td><td>470 (2.0)</td><td>174 (1.9)</td><td></td></tr><tr><td rowspan="4">Qualifications - visit 2, n (%)</td><td>other</td><td>45 (0.1)</td><td>26 (0.1)</td><td>19 (0.2)</td><td></td><td rowspan="4">&lt;0.001</td><td rowspan="4">Chi-squared</td><td rowspan="4">0.098</td></tr><tr><td>I have never smoked</td><td>15218 (46.8)</td><td>11345 (48.5)</td><td>3873 (42.6)</td><td></td></tr><tr><td>Just tried once or twice</td><td>5296 (16.3)</td><td>3802 (16.2)</td><td>1494 (16.4)</td><td></td></tr><tr><td>Smoked occasionally</td><td>4008 (12.3)</td><td>2881 (12.3)</td><td>1127 (12.4)</td><td></td></tr><tr><td rowspan="3">Qualifications - visit 2, n (%)</td><td>Smoked on most or all days other</td><td>7287 (22.4)</td><td>4949 (21.1)</td><td>2338 (25.7)</td><td></td><td rowspan="3">&lt;0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.098</td></tr><tr><td>0</td><td>689 (2.1)</td><td>436 (1.9)</td><td>253 (2.8)</td><td></td></tr><tr><td>A levels/AS levels or equivalent CSEs or equivalent</td><td>4013 (12.3)</td><td>2830 (12.1)</td><td>1183 (13.0)</td><td></td></tr><tr><td>Qualifications - visit 2, n (%)</td><td></td><td>1205 (3.7)</td><td>781 (3.3)</td><td>424 (4.7)</td><td></td><td></td><td></td><td></td></tr></tbody></table>
...continued

<table><caption>Table S9: Baseline characteristics of for the included participants, according to their life long depression status. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure having a lifelong depression). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No cMMD</th><th>cMMD</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="14"></td><td rowspan="14">Scanner lateral (x) brain position - visit 2, mean (SD)</td><td rowspan="14">College or University degree NVQ or HND or HNC or equivalent None of the above O levels/GCSEs or equivalent Other professional qualifications eg: nursing, teaching other</td><td>16203 (49.9)</td><td>11873 (50.7)</td><td>4330 (47.7)</td><td rowspan="14">0.047</td><td rowspan="14">Two Sample T-test</td><td rowspan="14">-0.024</td></tr><tr><td>1901 (5.8)</td><td>1397 (6.0)</td><td>504 (5.5)</td></tr><tr><td>1762 (5.4)</td><td>1257 (5.4)</td><td>505 (5.6)</td></tr><tr><td>5717 (17.6)</td><td>4018 (17.2)</td><td>1699 (18.7)</td></tr><tr><td>1596 (4.9)</td><td>1189 (5.1)</td><td>407 (4.5)</td></tr><tr><td>101 (0.3)</td><td>68 (0.3)</td><td>33 (0.4)</td></tr><tr><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.7 (3.0)</td></tr><tr><td>-28.1 (26.8)</td><td>-28.2 (26.7)</td><td>-27.8 (26.8)</td><td>0.280</td><td>Two Sample T-test</td><td>0.013</td></tr><tr><td>-1054.2 (25.1)</td><td>-1054.1 (25.0)</td><td>-1054.5 (25.3)</td><td>0.219</td><td>Two Sample T-test</td><td>-0.015</td></tr><tr><td>66.4 (5.9)</td><td>66.4 (5.9)</td><td>66.3 (5.9)</td><td>0.087</td><td>Two Sample T-test</td><td>-0.021</td></tr><tr><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.149</td><td>Two Sample T-test</td><td>0.018</td></tr><tr><td>17195 (52.9)</td><td>11600 (49.5)</td><td>5595 (61.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.244</td></tr><tr><td>15303 (47.1)</td><td>11813 (50.5)</td><td>3490 (38.4)</td><td rowspan="5">&lt;0.001</td><td rowspan="5">Chi-squared</td><td rowspan="5">0.124</td></tr><tr><td>1065 (3.3)</td><td>682 (2.9)</td><td>383 (4.2)</td></tr><tr><td>20503 (63.1)</td><td>15140 (64.7)</td><td>5363 (59.0)</td></tr><tr><td>10846 (33.4)</td><td>7532 (32.2)</td><td>3314 (36.5)</td></tr><tr><td>84 (0.3)</td><td>59 (0.3)</td><td>25 (0.3)</td></tr><tr><td>12720 (39.1)</td><td>8345 (35.6)</td><td>4375 (48.2)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.256</td></tr><tr><td>19778 (60.9)</td><td>15068 (64.4)</td><td>4710 (51.8)</td></tr><tr><td>13.1 (14.4)</td><td>13.2 (14.2)</td><td>12.9 (15.1)</td><td>0.093</td><td>Two Sample T-test</td><td>-0.021</td></tr><tr><td>-1.9 (2.7)</td><td>-2.0 (2.6)</td><td>-1.7 (2.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.119</td></tr><tr><td rowspan="3">Smoking status - visit 2, n (%)</td><td rowspan="3">Female Male Current Never Previous other False True</td><td>Cheadle</td><td>18991 (58.4)</td><td>13601 (58.1)</td><td>5390 (59.3)</td><td>0.087</td><td>Chi-squared</td><td>0.032</td></tr><tr><td>Newcastle</td><td>8436 (26.0)</td><td>6091 (26.0)</td><td>2345 (25.8)</td><td rowspan="3">&lt;0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.001</td></tr><tr><td>Reading other</td><td>5028 (15.5)</td><td>3691 (15.8)</td><td>1337 (14.7)</td></tr><tr><td rowspan="2">Social support, n (%)</td><td rowspan="2"></td><td></td><td>43 (0.1)</td><td>30 (0.1)</td><td>13 (0.1)</td><td rowspan="2"></td><td rowspan="2"></td></tr><tr><td></td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>1.3 (0.1)</td></tr><tr><td></td><td></td><td>Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No lifelong depression</th><th>Lifelong depression</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td>Sample size</td><td>n</td><td></td><td>32498</td><td>27461</td><td>5037</td><td></td><td></td><td></td></tr><tr><td rowspan="14">Outcome Mediators</td><td>G factor, mean (SD)</td><td></td><td>-0.0 (1.1)</td><td>-0.0 (1.2)</td><td>-0.1 (1.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.104</td></tr><tr><td>Dmri pc 0, mean (SD)</td><td></td><td>-0.3 (10.2)</td><td>-0.2 (10.3)</td><td>-1.0 (9.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.081</td></tr><tr><td>Dmri pc 1, mean (SD)</td><td></td><td>0.1 (5.2)</td><td>-0.0 (5.3)</td><td>0.6 (4.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.119</td></tr><tr><td>Dmri pc 2, mean (SD)</td><td></td><td>-0.1 (5.0)</td><td>-0.1 (5.1)</td><td>-0.3 (4.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.055</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td></td><td>0.0 (4.4)</td><td>0.0 (4.4)</td><td>-0.1 (4.3)</td><td>0.050</td><td>Two Sample T-test</td><td>-0.030</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td></td><td>0.0 (4.2)</td><td>-0.0 (4.2)</td><td>0.2 (4.2)</td><td>0.004</td><td>Two Sample T-test</td><td>0.044</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td></td><td>0.0 (3.4)</td><td>0.0 (3.4)</td><td>-0.0 (3.4)</td><td>0.857</td><td>Two Sample T-test</td><td>-0.003</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td></td><td>-0.4 (10.5)</td><td>-0.2 (10.6)</td><td>-1.0 (10.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.072</td></tr><tr><td>Smri dmri pc 1, mean (SD)</td><td></td><td>-0.2 (7.4)</td><td>-0.3 (7.5)</td><td>0.5 (7.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.109</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td></td><td>0.1 (5.6)</td><td>0.0 (5.6)</td><td>0.7 (5.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.131</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td></td><td>-0.0 (4.7)</td><td>0.0 (4.8)</td><td>-0.2 (4.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.052</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td></td><td>-0.0 (4.3)</td><td>-0.0 (4.3)</td><td>-0.0 (4.2)</td><td>0.882</td><td>Two Sample T-test</td><td>-0.002</td></tr><tr><td>Smri dmri pc 5, mean (SD)</td><td></td><td>0.0 (4.3)</td><td>0.0 (4.3)</td><td>0.2 (4.3)</td><td>0.013</td><td>Two Sample T-test</td><td>0.038</td></tr><tr><td>Smri pc 0, mean (SD)</td><td></td><td>0.3 (7.2)</td><td>0.3 (7.2)</td><td>-0.2 (7.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.071</td></tr><tr><td>Smri pc 1, mean (SD)</td><td></td><td>-0.0 (3.3)</td><td>0.0 (3.3)</td><td>-0.3 (3.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.093</td></tr><tr><td>Smri pc 2, mean (SD)</td><td></td><td>-0.1 (2.8)</td><td>0.0 (2.8)</td><td>-0.6 (2.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.208</td></tr><tr><td>Smri pc 3, mean (SD)</td><td></td><td>0.0 (2.1)</td><td>0.0 (2.1)</td><td>-0.0 (2.0)</td><td>0.774</td><td>Two Sample T-test</td><td>-0.004</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No lifelong depression</th><th>Lifelong depression</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="15">Confounders (alphabetic order)</td><td>Adopted as a child - visit 0, n (%)</td><td>No</td><td>32469 (99.9)</td><td>27434 (99.9)</td><td>5035 (100.0)</td><td>0.347</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>nan</td></tr><tr><td>Age when attended assessment centre - visit 2, mean (SD)</td><td>Yes<br/>other</td><td>9 (0.0)<br/>20 (0.1)<br/>63.7 (7.6)</td><td>9 (0.0)<br/>18 (0.1)<br/>64.0 (7.6)</td><td>2 (0.0)<br/>62.0 (7.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.272</td></tr><tr><td>Alcohol above nhs reco, n (%)</td><td>0<br/>1</td><td>21256 (65.4)<br/>11242 (34.6)</td><td>17744 (64.6)<br/>9717 (35.4)</td><td>3512 (69.7)<br/>1525 (30.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.109</td></tr><tr><td>Alcohol intake frequency - visit 2, n (%)</td><td>Daily or almost daily<br/>Never<br/>Once or twice a week<br/>One to three times a month<br/>Special occasions only<br/>Three or four times a week</td><td>5540 (17.0)<br/>2032 (6.3)<br/>8640 (26.6)<br/>3788 (11.7)<br/>3262 (10.0)<br/>9236 (28.4)</td><td>4752 (17.3)<br/>1661 (6.0)<br/>7420 (27.0)<br/>3111 (11.3)<br/>2581 (9.4)<br/>7936 (28.9)</td><td>788 (15.6)<br/>371 (7.4)<br/>1220 (24.2)<br/>677 (13.4)<br/>681 (13.5)<br/>1300 (25.8)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.172</td></tr><tr><td>Average total household income before tax - visit 2, n (%)</td><td>18,000 to 30,999</td><td>7813 (24.0)</td><td>6497 (23.7)</td><td>1316 (26.1)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.172</td></tr><tr><td>Body mass index (bmi) - visit 2, mean (SD)</td><td>31,000 to 51,999<br/>52,000 to 100,000<br/>Do not know<br/>Greater than 100,000<br/>Less than 18,000<br/>Prefer not to answer</td><td>9156 (28.2)<br/>7028 (21.6)<br/>961 (3.0)<br/>2277 (7.0)<br/>3402 (10.5)<br/>1861 (5.7)<br/>26.4 (4.3)</td><td>7802 (28.4)<br/>6032 (22.0)<br/>830 (3.0)<br/>1969 (7.2)<br/>2688 (9.8)<br/>1643 (6.0)<br/>26.3 (4.2)</td><td>1354 (26.9)<br/>996 (19.8)<br/>131 (2.6)<br/>308 (6.1)<br/>714 (14.2)<br/>218 (4.3)<br/>26.9 (4.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.118</td></tr><tr><td>Breastfed as a baby - visit 0, n (%)</td><td>Do not know</td><td>6175 (19.0)</td><td>5360 (19.5)</td><td>815 (16.2)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.092</td></tr><tr><td>Comparative body size at age 10 - visit 0, n (%)</td><td>No<br/>Yes<br/>other<br/>About average</td><td>7174 (22.1)<br/>19136 (58.9)<br/>13 (0.0)<br/>16637 (51.2)</td><td>5978 (21.8)<br/>16113 (58.7)<br/>10 (0.0)<br/>14294 (52.1)</td><td>1196 (23.7)<br/>3023 (60.0)<br/>3 (0.1)<br/>2343 (46.5)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.138</td></tr><tr><td>Comparative height size at age 10 - visit 0, n (%)</td><td>Do not know<br/>Plumper<br/>Thinner<br/>other<br/>About average</td><td>347 (1.1)<br/>4922 (15.1)<br/>10584 (32.6)<br/>8 (0.0)<br/>17039 (52.4)</td><td>303 (1.1)<br/>3972 (14.5)<br/>8886 (32.4)<br/>6 (0.0)<br/>14555 (53.0)</td><td>44 (0.9)<br/>950 (18.9)<br/>1698 (33.7)<br/>2 (0.0)<br/>2484 (49.3)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.090</td></tr><tr><td>Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>Do not know<br/>Shorter<br/>Taller<br/>other<br/>Elsewhere</td><td>293 (0.9)<br/>6569 (20.2)<br/>8589 (26.4)<br/>8 (0.0)<br/>1778 (5.5)</td><td>262 (1.0)<br/>5445 (19.8)<br/>7193 (26.2)<br/>6 (0.0)<br/>1535 (5.6)</td><td>31 (0.6)<br/>1124 (22.3)<br/>1396 (27.7)<br/>2 (0.0)<br/>243 (4.8)</td><td>0.070</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.053</td></tr><tr><td>Current employment status - visit 2, n (%)</td><td>England<br/>Northern Ireland<br/>Republic of Ireland<br/>Scotland<br/>Wales<br/>other<br/>In paid employment or self-employed</td><td>27360 (84.2)<br/>234 (0.7)<br/>217 (0.7)<br/>2296 (7.1)<br/>600 (1.8)<br/>13 (0.0)<br/>12978 (39.9)</td><td>23043 (83.9)<br/>196 (0.7)<br/>189 (0.7)<br/>1974 (7.2)<br/>513 (1.9)<br/>11 (0.0)<br/>10755 (39.2)</td><td>4317 (85.7)<br/>38 (0.8)<br/>28 (0.6)<br/>322 (6.4)<br/>87 (1.7)<br/>2 (0.0)<br/>2223 (44.1)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.177</td></tr><tr><td>Current smoker, n (%)</td><td>Retired<br/>other</td><td>18302 (56.3)<br/>1218 (3.7)</td><td>15787 (57.5)<br/>919 (3.3)</td><td>2515 (49.9)<br/>299 (5.9)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.053</td></tr><tr><td>Current tobacco smoking - visit 2, n (%)</td><td>0<br/>1<br/>No<br/>Yes, on most or all days<br/>other</td><td>31893 (98.1)<br/>605 (1.9)<br/>31431 (96.7)<br/>605 (1.9)<br/>462 (1.4)</td><td>26982 (98.3)<br/>479 (1.7)<br/>26600 (96.9)<br/>479 (1.7)<br/>382 (1.4)</td><td>4911 (97.5)<br/>126 (2.5)<br/>4831 (95.9)<br/>126 (2.5)<br/>80 (1.6)</td><td>0.001</td><td>Chi-squared</td><td>0.055</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No lifelong depression</th><th>Lifelong depression</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="12"></td><td>Diabetic, n (%)</td><td>0</td><td>31154 (95.9)</td><td>26318 (95.8)</td><td>4836 (96.0)</td><td rowspan="12">0.600</td><td rowspan="12">Chi-squared</td><td rowspan="12">0.009</td></tr><tr><td rowspan="3">Ethnic background - visit 2, n (%)</td><td>1</td><td>1344 (4.1)</td><td>1143 (4.2)</td><td>201 (4.0)</td></tr><tr><td>British</td><td>7408 (22.8)</td><td>6087 (22.2)</td><td>1321 (26.2)</td></tr><tr><td>other</td><td>25090 (77.2)</td><td>21374 (77.8)</td><td>3716 (73.8)</td></tr><tr><td rowspan="3">Ever smoked - visit 2, n (%)</td><td>No</td><td>15217 (46.8)</td><td>13109 (47.7)</td><td>2108 (41.9)</td></tr><tr><td>Yes</td><td>17196 (52.9)</td><td>14279 (52.0)</td><td>2917 (57.9)</td></tr><tr><td>other</td><td>85 (0.3)</td><td>73 (0.3)</td><td>12 (0.2)</td></tr><tr><td rowspan="2">Handedness (chirality/laterality) - visit 0, n (%)</td><td>Left-handed</td><td>3043 (9.4)</td><td>2597 (9.5)</td><td>446 (8.9)</td></tr><tr><td>Right-handed</td><td>28957 (89.1)</td><td>24438 (89.0)</td><td>4519 (89.7)</td></tr><tr><td rowspan="3">Hypercholesterol, n (%)</td><td>Use both right and left hands equally</td><td>486 (1.5)</td><td>417 (1.5)</td><td>69 (1.4)</td></tr><tr><td>other</td><td>12 (0.0)</td><td>9 (0.0)</td><td>3 (0.1)</td></tr><tr><td>0</td><td>24538 (75.5)</td><td>20609 (75.0)</td><td>3929 (78.0)</td></tr><tr><td rowspan="2">Hypertensive, n (%)</td><td>1</td><td>7960 (24.5)</td><td>6852 (25.0)</td><td>1108 (22.0)</td></tr><tr><td>0</td><td>23962 (73.7)</td><td>20138 (73.3)</td><td>3824 (75.9)</td></tr><tr><td rowspan="2">Inflammation, n (%)</td><td>1</td><td>8536 (26.3)</td><td>7323 (26.7)</td><td>1213 (24.1)</td></tr><tr><td>False</td><td>27267 (83.9)</td><td>23161 (84.3)</td><td>4106 (81.5)</td></tr><tr><td rowspan="3">Job involves shift work - visit 2, n (%)</td><td>True</td><td>5231 (16.1)</td><td>4300 (15.7)</td><td>931 (18.5)</td></tr><tr><td>Always</td><td>795 (2.4)</td><td>656 (2.4)</td><td>139 (2.8)</td></tr><tr><td>Never/rarely</td><td>11077 (34.1)</td><td>9200 (33.5)</td><td>1877 (37.3)</td></tr><tr><td rowspan="2">Length of time at current address - visit 2, mean (SD)</td><td>Sometimes</td><td>855 (2.6)</td><td>691 (2.5)</td><td>164 (3.3)</td></tr><tr><td>other</td><td>19771 (60.8)</td><td>16914 (61.6)</td><td>2857 (56.7)</td></tr><tr><td>Ls pc dim.1, mean (SD)</td><td></td><td>21.0 (13.9)</td><td>21.4 (13.9)</td><td>18.7 (13.5)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.200</td></tr><tr><td>Ls pc dim.2, mean (SD)</td><td></td><td>0.6 (2.0)</td><td>0.7 (2.0)</td><td>0.4 (2.1)</td></tr><tr><td>Maternal smoking around birth - visit 0, n (%)</td><td>Do not know</td><td>3388 (10.4)</td><td>2900 (10.6)</td><td>488 (9.7)</td><td>0.002</td><td>Two Sample T-test</td><td>-0.118</td></tr><tr><td rowspan="2">Number in household - visit 2, mean (SD)</td><td>No</td><td>20344 (62.6)</td><td>17260 (62.9)</td><td>3084 (61.2)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.079</td></tr><tr><td>Yes</td><td>8749 (26.9)</td><td>7286 (26.5)</td><td>1463 (29.0)</td></tr><tr><td>Number of full brothers - visit 2, mean (SD)</td><td>other</td><td>17 (0.1)</td><td>15 (0.1)</td><td>2 (0.0)</td><td rowspan="2">0.247</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.018</td></tr><tr><td>Number of full sisters - visit 2, mean (SD)</td><td></td><td>2.2 (1.0)</td><td>2.2 (1.0)</td><td>2.1 (1.1)</td></tr><tr><td>Number of vehicles in household - visit 2, n (%)</td><td>Four or more</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>0.208</td><td>Two Sample T-test</td><td>0.020</td></tr><tr><td rowspan="2">Obesity, n (%)</td><td></td><td>922 (2.8)</td><td>788 (2.9)</td><td>134 (2.7)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.149</td></tr><tr><td></td><td>None</td><td>1265 (3.9)</td><td>978 (3.6)</td><td>287 (5.7)</td></tr><tr><td rowspan="4">Part of a multiple birth - visit 0, n (%)</td><td></td><td>One</td><td>13770 (42.4)</td><td>11454 (41.7)</td><td>2316 (46.0)</td><td rowspan="4">&lt;0.001</td><td rowspan="4">Chi-squared</td><td rowspan="4">0.111</td></tr><tr><td></td><td>Three</td><td>3034 (9.3)</td><td>2610 (9.5)</td><td>424 (8.4)</td></tr><tr><td></td><td>Two</td><td>13471 (41.5)</td><td>11599 (42.2)</td><td>1872 (37.2)</td></tr><tr><td></td><td>other</td><td>36 (0.1)</td><td>32 (0.1)</td><td>4 (0.1)</td></tr><tr><td rowspan="3">Past tobacco smoking - visit 2, n (%)</td><td></td><td>0</td><td>26781 (82.4)</td><td>22816 (83.1)</td><td>3965 (78.7)</td><td rowspan="3">&lt;0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.012</td></tr><tr><td></td><td>1</td><td>5717 (17.6)</td><td>4645 (16.9)</td><td>1072 (21.3)</td></tr><tr><td></td><td>No</td><td>31809 (97.9)</td><td>26874 (97.9)</td><td>4935 (98.0)</td></tr><tr><td rowspan="5">Qualifications - visit 2, n (%)</td><td></td><td>Yes</td><td>644 (2.0)</td><td>550 (2.0)</td><td>94 (1.9)</td><td rowspan="5">&lt;0.001</td><td rowspan="5">Chi-squared</td><td rowspan="5">0.140</td></tr><tr><td></td><td>other</td><td>45 (0.1)</td><td>37 (0.1)</td><td>8 (0.2)</td></tr><tr><td>I have never smoked</td><td>15218 (46.8)</td><td>13110 (47.7)</td><td>2108 (41.9)</td></tr><tr><td>Just tried once or twice</td><td>5296 (16.3)</td><td>4437 (16.2)</td><td>859 (17.1)</td></tr><tr><td>Smoked occasionally</td><td>4008 (12.3)</td><td>3402 (12.4)</td><td>606 (12.0)</td></tr><tr><td rowspan="4"></td><td></td><td>Smoked on most or all days</td><td>7287 (22.4)</td><td>5961 (21.7)</td><td>1326 (26.3)</td><td rowspan="4">&lt;0.001</td><td rowspan="4">Chi-squared</td><td rowspan="4">0.133</td></tr><tr><td></td><td>other</td><td>689 (2.1)</td><td>551 (2.0)</td><td>138 (2.7)</td></tr><tr><td>A levels/AS levels or equivalent</td><td>4013 (12.3)</td><td>3333 (12.1)</td><td>680 (13.5)</td></tr><tr><td>CSEs or equivalent</td><td>1205 (3.7)</td><td>1028 (3.7)</td><td>177 (3.5)</td></tr><tr><td rowspan="3"></td><td></td><td>College or University degree</td><td>16203 (49.9)</td><td>13538 (49.3)</td><td>2665 (52.9)</td><td rowspan="3">&lt;0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.133</td></tr><tr><td></td><td>NVQ or HND or HNC or equivalent</td><td>1901 (5.8)</td><td>1672 (6.1)</td><td>229 (4.5)</td></tr><tr><td></td><td>None of the above</td><td>1762 (5.4)</td><td>1571 (5.7)</td><td>191 (3.8)</td></tr><tr><td></td><td>O levels/GCSEs or equivalent</td><td>5717 (17.6)</td><td>4863 (17.7)</td><td>854 (17.0)</td><td></td><td></td><td></td></tr></tbody></table>
...continued

<table><caption>Table S10: Baseline characteristics of the included participants, according to their social support status. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure having a good social support). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No lifelong depression</th><th>Lifelong depression</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="11"></td><td rowspan="3">Scanner lateral (x) brain position - visit 2, mean (SD)</td><td rowspan="3">Other professional qualifications eg: nursing, teaching other</td><td>1596 (4.9)</td><td>1365 (5.0)</td><td>231 (4.6)</td><td></td><td></td><td></td></tr><tr><td>101 (0.3)</td><td>91 (0.3)</td><td>10 (0.2)</td><td></td><td></td><td></td></tr><tr><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.7 (2.9)</td><td>0.150</td><td>Two Sample T-test</td><td>-0.022</td></tr><tr><td rowspan="2">Scanner longitudinal (z) brain position - visit 2, mean (SD)</td><td></td><td>-28.1 (26.8)</td><td>-28.4 (26.6)</td><td>-26.3 (27.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.076</td></tr><tr><td></td><td>-1054.2 (25.1)</td><td>-1054.0 (24.9)</td><td>-1055.7 (26.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.070</td></tr><tr><td rowspan="2">Scanner table position - visit 2, mean (SD)</td><td></td><td>66.4 (5.9)</td><td>66.5 (5.9)</td><td>65.9 (6.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.094</td></tr><tr><td></td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.830</td><td>Two Sample T-test</td><td>0.003</td></tr><tr><td rowspan="2">Scanner transverse (y) brain position - visit 2, mean (SD)</td><td></td><td>17195 (52.9)</td><td>13808 (50.3)</td><td>3387 (67.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.350</td></tr><tr><td></td><td>15303 (47.1)</td><td>13653 (49.7)</td><td>1650 (32.8)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Self declared mental exclusion visit 2, mean (SD)</td><td>Female</td><td></td><td>1065 (3.3)</td><td>859 (3.1)</td><td>206 (4.1)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.106</td></tr><tr><td>Male</td><td></td><td>20503 (63.1)</td><td>17536 (63.9)</td><td>2967 (58.9)</td><td></td><td></td><td></td></tr><tr><td>Current</td><td></td><td>10846 (33.4)</td><td>8994 (32.8)</td><td>1852 (36.8)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Smoking status - visit 2, n (%)</td><td>Never</td><td></td><td>84 (0.3)</td><td>72 (0.3)</td><td>12 (0.2)</td><td></td><td></td><td></td></tr><tr><td>Previous other</td><td></td><td>12720 (39.1)</td><td>10550 (38.4)</td><td>2170 (43.1)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.095</td></tr><tr><td rowspan="2">Social support, n (%)</td><td>False</td><td></td><td>19778 (60.9)</td><td>16911 (61.6)</td><td>2867 (56.9)</td><td></td><td></td><td></td></tr><tr><td>True</td><td></td><td>13.1 (14.4)</td><td>13.3 (14.4)</td><td>11.9 (14.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.099</td></tr><tr><td rowspan="2">Total alcohol weekly units 2, mean (SD)</td><td></td><td></td><td>-1.9 (2.7)</td><td>-2.0 (2.7)</td><td>-1.6 (2.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.126</td></tr><tr><td></td><td></td><td>18991 (58.4)</td><td>15890 (57.9)</td><td>3101 (61.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.082</td></tr><tr><td rowspan="2">Townsend deprivation index at recruitment - visit 0, mean (SD)</td><td></td><td>Cheadle</td><td>8436 (26.0)</td><td>7203 (26.2)</td><td>1233 (24.5)</td><td></td><td></td><td></td></tr><tr><td></td><td>Newcastle</td><td>5028 (15.5)</td><td>4335 (15.8)</td><td>693 (13.8)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Uk biobank assessment centre - visit 2, n (%)</td><td></td><td>Reading other</td><td>43 (0.1)</td><td>33 (0.1)</td><td>10 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.211</td></tr><tr><td rowspan="11"></td><td rowspan="11">Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td rowspan="11">Other professional qualifications eg: nursing, teaching other</td><td></td><td>32498</td><td>12720</td><td>19778</td><td></td><td></td><td></td></tr><tr><td></td><td>-0.0 (1.1)</td><td>0.0 (1.2)</td><td>-0.1 (1.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.072</td></tr><tr><td></td><td>-0.3 (10.2)</td><td>0.2 (10.4)</td><td>-0.6 (10.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.084</td></tr><tr><td></td><td>0.1 (5.2)</td><td>-0.1 (5.3)</td><td>0.2 (5.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.068</td></tr><tr><td></td><td>-0.1 (5.0)</td><td>0.1 (5.0)</td><td>-0.2 (5.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.063</td></tr><tr><td></td><td>0.0 (4.4)</td><td>0.0 (4.5)</td><td>0.0 (4.3)</td><td>0.732</td><td>Two Sample T-test</td><td>-0.004</td></tr><tr><td></td><td>0.0 (4.2)</td><td>0.0 (4.4)</td><td>0.0 (4.1)</td><td>0.649</td><td>Two Sample T-test</td><td>-0.005</td></tr><tr><td></td><td>0.0 (3.4)</td><td>0.0 (3.5)</td><td>0.0 (3.4)</td><td>0.729</td><td>Two Sample T-test</td><td>-0.004</td></tr><tr><td></td><td>-0.4 (10.5)</td><td>0.2 (10.7)</td><td>-0.7 (10.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.093</td></tr><tr><td></td><td>-0.2 (7.4)</td><td>-0.1 (7.5)</td><td>-0.2 (7.4)</td><td>0.494</td><td>Two Sample T-test</td><td>-0.008</td></tr><tr><td></td><td>0.1 (5.6)</td><td>-0.2 (5.7)</td><td>0.3 (5.5)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.091</td></tr><tr><td></td><td>-0.0 (4.7)</td><td>0.0 (4.7)</td><td>-0.0 (4.7)</td><td>0.259</td><td>Two Sample T-test</td><td>-0.013</td></tr><tr><td></td><td>-0.0 (4.3)</td><td>0.0 (4.4)</td><td>-0.0 (4.3)</td><td>0.151</td><td>Two Sample T-test</td><td>-0.016</td></tr><tr><td></td><td>0.0 (4.3)</td><td>0.0 (4.4)</td><td>0.0 (4.2)</td><td>0.679</td><td>Two Sample T-test</td><td>0.005</td></tr><tr><td></td><td>0.3 (7.2)</td><td>0.1 (7.2)</td><td>0.4 (7.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.045</td></tr><tr><td></td><td>-0.0 (3.3)</td><td>0.1 (3.3)</td><td>-0.1 (3.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.066</td></tr><tr><td></td><td>-0.1 (2.8)</td><td>0.1 (2.8)</td><td>-0.2 (2.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.122</td></tr><tr><td></td><td>0.0 (2.1)</td><td>0.0 (2.1)</td><td>-0.0 (2.0)</td><td>0.019</td><td>Two Sample T-test</td><td>-0.027</td></tr><tr><td rowspan="2">Confounders (alphabetic order)</td><td rowspan="2">Adopted as a child - visit 0, n (%)</td><td>No</td><td>32469 (99.9)</td><td>12706 (99.9)</td><td>19763 (99.9)</td><td>0.014</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.033</td></tr><tr><td>Yes</td><td>9 (0.0)</td><td>1 (0.0)</td><td>8 (0.0)</td><td></td><td></td><td></td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Lack of social support</th><th>Social support</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="11">Sample size<br>Outcome<br>Mediators</td><td rowspan="11">n</td><td>G factor, mean (SD)</td><td></td><td>32498</td><td>12720</td><td>19778</td><td></td><td></td><td></td></tr><tr><td>Dmri pc 0, mean (SD)</td><td></td><td>-0.0 (1.1)</td><td>0.0 (1.2)</td><td>-0.1 (1.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.072</td></tr><tr><td>Dmri pc 1, mean (SD)</td><td></td><td>-0.3 (10.2)</td><td>0.2 (10.4)</td><td>-0.6 (10.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.084</td></tr><tr><td>Dmri pc 2, mean (SD)</td><td></td><td>0.1 (5.2)</td><td>-0.1 (5.3)</td><td>0.2 (5.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.068</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td></td><td>-0.1 (5.0)</td><td>0.1 (5.0)</td><td>-0.2 (5.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.063</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td></td><td>0.0 (4.4)</td><td>0.0 (4.5)</td><td>0.0 (4.3)</td><td>0.732</td><td>Two Sample T-test</td><td>-0.004</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td></td><td>0.0 (4.2)</td><td>0.0 (4.4)</td><td>0.0 (4.1)</td><td>0.649</td><td>Two Sample T-test</td><td>-0.005</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td></td><td>0.0 (3.4)</td><td>0.0 (3.5)</td><td>0.0 (3.4)</td><td>0.729</td><td>Two Sample T-test</td><td>-0.004</td></tr><tr><td>Smri dmri pc 1, mean (SD)</td><td></td><td>-0.4 (10.5)</td><td>0.2 (10.7)</td><td>-0.7 (10.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.093</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td></td><td>-0.2 (7.4)</td><td>-0.1 (7.5)</td><td>-0.2 (7.4)</td><td>0.494</td><td>Two Sample T-test</td><td>-0.008</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td></td><td>0.1 (5.6)</td><td>-0.2 (5.7)</td><td>0.3 (5.5)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.091</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td></td><td>-0.0 (4.7)</td><td>0.0 (4.7)</td><td>-0.0 (4.7)</td><td>0.259</td><td>Two Sample T-test</td><td>-0.013</td></tr><tr><td>Smri dmri pc 5, mean (SD)</td><td></td><td>-0.0 (4.3)</td><td>0.0 (4.4)</td><td>-0.0 (4.3)</td><td>0.151</td><td>Two Sample T-test</td><td>-0.016</td></tr><tr><td>Smri pc 0, mean (SD)</td><td></td><td>0.0 (4.3)</td><td>0.0 (4.4)</td><td>0.0 (4.2)</td><td>0.679</td><td>Two Sample T-test</td><td>0.005</td></tr><tr><td>Smri pc 1, mean (SD)</td><td></td><td>0.3 (7.2)</td><td>0.1 (7.2)</td><td>0.4 (7.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.045</td></tr><tr><td>Smri pc 2, mean (SD)</td><td></td><td>-0.0 (3.3)</td><td>0.1 (3.3)</td><td>-0.1 (3.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.066</td></tr><tr><td>Smri pc 3, mean (SD)</td><td></td><td>-0.1 (2.8)</td><td>0.1 (2.8)</td><td>-0.2 (2.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.122</td></tr><tr><td rowspan="2">Confounders (alphabetic order)</td><td rowspan="2">Adopted as a child - visit 0, n (%)</td><td>No</td><td>32469 (99.9)</td><td>12706 (99.9)</td><td>19763 (99.9)</td><td>0.014</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.033</td></tr><tr><td>Yes</td><td>9 (0.0)</td><td>1 (0.0)</td><td>8 (0.0)</td><td></td><td></td><td></td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Lack of social support</th><th>Social support</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10"></td><td>Age when attended assessment centre - visit 2, mean (SD)</td><td>other</td><td>20 (0.1)<br>63.7 (7.6)</td><td>13 (0.1)<br>64.3 (7.6)</td><td>7 (0.0)<br>63.3 (7.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.127</td></tr><tr><td>Alcohol above nhs reco, n (%)</td><td>0<br>1</td><td>21256 (65.4)<br>11242 (34.6)</td><td>8371 (65.8)<br>4349 (34.2)</td><td>12885 (65.1)<br>6893 (34.9)</td><td>0.226</td><td>Chi-squared</td><td>0.014</td></tr><tr><td>Alcohol intake frequency - visit 2, n (%)</td><td>Daily or almost daily<br>Never<br>Once or twice a week<br>One to three times a month<br>Special occasions only<br>Three or four times a week</td><td>5540 (17.0)<br>2032 (6.3)<br>8640 (26.6)<br>3788 (11.7)<br>3262 (10.0)<br>9236 (28.4)<br>18,000 to 30,999</td><td>2169 (17.1)<br>858 (6.7)<br>3264 (25.7)<br>1630 (12.8)<br>1444 (11.4)<br>3355 (26.4)<br>3309 (26.0)</td><td>3371 (17.0)<br>1174 (5.9)<br>5376 (27.2)<br>2158 (10.9)<br>1818 (9.2)<br>5881 (29.7)<br>4504 (22.8)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.117</td></tr><tr><td>Average total household income before tax - visit 2, n (%)</td><td>31,000 to 51,999<br>52,000 to 100,000<br>Do not know<br>Greater than 100,000<br>Less than 18,000<br>Prefer not to answer</td><td>9156 (28.2)<br>7028 (21.6)<br>961 (3.0)<br>2277 (7.0)<br>3402 (10.5)<br>1861 (5.7)<br>26.4 (4.3)</td><td>3445 (27.1)<br>2421 (19.0)<br>384 (3.0)<br>689 (5.4)<br>1746 (13.7)<br>726 (5.7)<br>26.5 (4.4)</td><td>5711 (28.9)<br>4607 (23.3)<br>577 (2.9)<br>1588 (8.0)<br>1656 (8.4)<br>1135 (5.7)<br>26.4 (4.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.225</td></tr><tr><td>Body mass index (bmi) - visit 2, mean (SD)</td><td>Do not know</td><td>6175 (19.0)<br>7174 (22.1)<br>19136 (58.9)<br>13 (0.0)</td><td>2710 (21.3)<br>2605 (20.5)<br>7400 (58.2)<br>5 (0.0)</td><td>3465 (17.5)<br>4569 (23.1)<br>11736 (59.3)<br>8 (0.0)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.104</td></tr><tr><td>Breastfed as a baby - visit 0, n (%)</td><td>No<br>Yes<br>other</td><td>23413 (72.0)<br>9085 (28.0)<br>16637 (51.2)</td><td>8345 (65.6)<br>4375 (34.4)<br>6419 (50.5)</td><td>15068 (76.2)<br>4710 (23.8)<br>10218 (51.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.235</td></tr><tr><td>Cmdd final, n (%)</td><td>False<br>True</td><td></td><td></td><td></td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.058</td></tr><tr><td>Comparative body size at age 10 - visit 0, n (%)</td><td>About average</td><td></td><td></td><td></td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.052</td></tr><tr><td>Comparative height size at age 10 - visit 0, n (%)</td><td>Do not know<br>Plumper<br>Thinner<br>other<br>About average</td><td>347 (1.1)<br>4922 (15.1)<br>10584 (32.6)<br>8 (0.0)<br>17039 (52.4)</td><td>178 (1.4)<br>1982 (15.6)<br>4137 (32.5)<br>4 (0.0)<br>6647 (52.3)</td><td>169 (0.9)<br>2940 (14.9)<br>6447 (32.6)<br>4 (0.0)<br>10392 (52.5)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.052</td></tr><tr><td>Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>Do not know<br>Shorter<br>Taller<br>other<br>Elsewhere</td><td>293 (0.9)<br>6569 (20.2)<br>8589 (26.4)<br>8 (0.0)<br>1778 (5.5)</td><td>149 (1.2)<br>2627 (20.7)<br>3293 (25.9)<br>4 (0.0)<br>789 (6.2)</td><td>144 (0.7)<br>3942 (19.9)<br>5296 (26.8)<br>4 (0.0)<br>989 (5.0)</td><td>0.001</td><td>Chi-squared</td><td>0.055</td></tr><tr><td rowspan="5"></td><td>Current employment status - visit 2, n (%)</td><td>England<br>Northern Ireland<br>Republic of Ireland<br>Scotland<br>Wales<br>other<br>In paid employment or self-employed</td><td>27360 (84.2)<br>234 (0.7)<br>217 (0.7)<br>2296 (7.1)<br>600 (1.8)<br>13 (0.0)<br>12978 (39.9)</td><td>10607 (83.4)<br>90 (0.7)<br>87 (0.7)<br>909 (7.1)<br>231 (1.8)<br>7 (0.1)<br>4969 (39.1)</td><td>16753 (84.7)<br>144 (0.7)<br>130 (0.7)<br>1387 (7.0)<br>369 (1.9)<br>6 (0.0)<br>8009 (40.5)</td><td>0.020</td><td>Chi-squared</td><td>0.032</td></tr><tr><td>Current smoker, n (%)</td><td>Retired<br>other</td><td>18302 (56.3)<br>1218 (3.7)<br>31893 (98.1)<br>605 (1.9)</td><td>7249 (57.0)<br>502 (3.9)<br>12461 (98.0)<br>259 (2.0)</td><td>11053 (55.9)<br>716 (3.6)<br>19432 (98.3)<br>346 (1.7)</td><td>0.068</td><td>Chi-squared</td><td>0.021</td></tr><tr><td>Current tobacco smoking - visit 2, n (%)</td><td>No<br>Yes, on most or all days<br>other</td><td>31431 (96.7)<br>605 (1.9)<br>462 (1.4)<br>31154 (95.9)<br>1344 (4.1)</td><td>12263 (96.4)<br>259 (2.0)<br>198 (1.6)<br>12122 (95.3)<br>598 (4.7)</td><td>19168 (96.9)<br>346 (1.7)<br>264 (1.3)<br>19032 (96.2)<br>746 (3.8)</td><td>0.043</td><td>Chi-squared</td><td>0.028</td></tr><tr><td>Diabetic, n (%)</td><td>0<br>1</td><td>7408 (22.8)<br>25090 (77.2)</td><td>2900 (22.8)<br>9820 (77.2)</td><td>4508 (22.8)<br>15270 (77.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.046</td></tr><tr><td>Ethnic background - visit 2, n (%)</td><td>British<br>other</td><td>15217 (46.8)</td><td>5829 (45.8)</td><td>9388 (47.5)</td><td>1.000</td><td>Chi-squared</td><td>&lt;0.001</td></tr><tr><td></td><td>Ever smoked - visit 2, n (%)</td><td>No</td><td></td><td></td><td></td><td>0.008</td><td>Chi-squared</td><td>0.035</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Lack of social support</th><th>Social support</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="2">Handedness (chirality/laterality) - visit 0, n (%)</td><td>Yes</td><td>Yes</td><td>17196 (52.9)</td><td>6852 (53.9)</td><td>10344 (52.3)</td><td rowspan="2">0.435</td><td rowspan="2">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="2">0.018</td></tr><tr><td>other</td><td>other</td><td>85 (0.3)</td><td>39 (0.3)</td><td>46 (0.2)</td></tr><tr><td></td><td>Left-handed</td><td>Left-handed</td><td>3043 (9.4)</td><td>1205 (9.5)</td><td>1838 (9.3)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Hypercholesterol, n (%)</td><td>Right-handed</td><td>Right-handed</td><td>28957 (89.1)</td><td>11310 (88.9)</td><td>17647 (89.2)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.047</td></tr><tr><td>Use both right and left hands equally</td><td>Use both right and left hands equally</td><td>486 (1.5)</td><td>198 (1.6)</td><td>288 (1.5)</td></tr><tr><td rowspan="2">Hypertensive, n (%)</td><td>other</td><td>other</td><td>12 (0.0)</td><td>7 (0.1)</td><td>5 (0.0)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.060</td></tr><tr><td>0</td><td>0</td><td>9447 (74.3)</td><td>15091 (76.3)</td><td>4687 (23.7)</td></tr><tr><td rowspan="2">Inflammation, n (%)</td><td>0</td><td>1</td><td>7960 (24.5)</td><td>3273 (25.7)</td><td>14787 (74.8)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.038</td></tr><tr><td>1</td><td>1</td><td>23962 (73.7)</td><td>9175 (72.1)</td><td>4991 (25.2)</td></tr><tr><td rowspan="2">Job involves shift work - visit 2, n (%)</td><td>False</td><td>False</td><td>27267 (83.9)</td><td>10565 (83.1)</td><td>16702 (84.4)</td><td rowspan="2">0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.047</td></tr><tr><td>True</td><td>True</td><td>5231 (16.1)</td><td>2155 (16.9)</td><td>3076 (15.6)</td></tr><tr><td rowspan="3">Length of time at current address - visit 2, mean (SD)</td><td>Always</td><td>Always</td><td>795 (2.4)</td><td>336 (2.6)</td><td>459 (2.3)</td><td rowspan="3">0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.047</td></tr><tr><td>Never/rarely</td><td>Never/rarely</td><td>11077 (34.1)</td><td>4179 (32.9)</td><td>6898 (34.9)</td></tr><tr><td>Sometimes</td><td>Sometimes</td><td>855 (2.6)</td><td>352 (2.8)</td><td>503 (2.5)</td></tr><tr><td rowspan="2">Life long depression, n (%)</td><td>other</td><td>other</td><td>19771 (60.8)</td><td>7853 (61.7)</td><td>11918 (60.3)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.059</td></tr><tr><td>False</td><td>False</td><td>27461 (84.5)</td><td>10550 (82.9)</td><td>16911 (85.5)</td></tr><tr><td rowspan="2">Ls pc dim.1, mean (SD)</td><td>True</td><td>True</td><td>5037 (15.5)</td><td>2170 (17.1)</td><td>2867 (14.5)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.070</td></tr><tr><td>0</td><td>0</td><td>0.6 (2.0)</td><td>0.4 (2.1)</td><td>0.7 (2.0)</td></tr><tr><td rowspan="2">Ls pc dim.2, mean (SD)</td><td>0</td><td>0</td><td>-0.4 (2.0)</td><td>-0.4 (2.0)</td><td>-0.5 (2.0)</td><td rowspan="2">0.015</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.152</td></tr><tr><td>1</td><td>1</td><td>3388 (10.4)</td><td>1447 (11.4)</td><td>1941 (9.8)</td></tr><tr><td rowspan="2">Maternal smoking around birth - visit 0, n (%)</td><td>Do not know</td><td>Do not know</td><td></td><td></td><td></td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.052</td></tr><tr><td>No</td><td>No</td><td>20344 (62.6)</td><td>7902 (62.1)</td><td>12442 (62.9)</td></tr><tr><td rowspan="2">Mh pc dim.1, mean (SD)</td><td>Yes</td><td>Yes</td><td>8749 (26.9)</td><td>3366 (26.5)</td><td>5383 (27.2)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.301</td></tr><tr><td>other</td><td>other</td><td>17 (0.1)</td><td>5 (0.0)</td><td>12 (0.1)</td></tr><tr><td rowspan="2">Mh pc dim.2, mean (SD)</td><td></td><td></td><td>1.0 (6.5)</td><td>-0.2 (6.8)</td><td>1.8 (6.2)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.146</td></tr><tr><td></td><td></td><td>0.5 (3.3)</td><td>0.2 (3.4)</td><td>0.6 (3.2)</td></tr><tr><td rowspan="2">Number in household - visit 2, mean (SD)</td><td></td><td></td><td>2.2 (1.0)</td><td>2.0 (1.1)</td><td>2.2 (0.9)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.195</td></tr><tr><td></td><td></td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td></tr><tr><td>Number of full brothers - visit 2, mean (SD)</td><td></td><td></td><td></td><td></td><td></td><td>0.618</td><td></td><td></td></tr><tr><td>Number of full sisters - visit 2, mean (SD)</td><td></td><td></td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>0.350</td><td></td><td></td></tr><tr><td>Number of vehicles in household - visit 2, n (%)</td><td>Four or more</td><td>Four or more</td><td>922 (2.8)</td><td>353 (2.8)</td><td>569 (2.9)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.199</td></tr><tr><td rowspan="2">Obesity, n (%)</td><td>None</td><td>None</td><td>1265 (3.9)</td><td>688 (5.4)</td><td>577 (2.9)</td><td rowspan="2">0.022</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.026</td></tr><tr><td>One</td><td>One</td><td>13770 (42.4)</td><td>5870 (46.1)</td><td>7900 (39.9)</td></tr><tr><td rowspan="2">Part of a multiple birth - visit 0, n (%)</td><td>Three</td><td>Three</td><td>3034 (9.3)</td><td>1035 (8.1)</td><td>1999 (10.1)</td><td rowspan="2">0.620</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.011</td></tr><tr><td>Two</td><td>Two</td><td>13471 (41.5)</td><td>4758 (37.4)</td><td>8713 (44.1)</td></tr><tr><td rowspan="2">Past tobacco smoking - visit 2, n (%)</td><td>other</td><td>other</td><td>36 (0.1)</td><td>16 (0.1)</td><td>20 (0.1)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.060</td></tr><tr><td>0</td><td>0</td><td>26781 (82.4)</td><td>10405 (81.8)</td><td>16376 (82.8)</td></tr><tr><td rowspan="2">Qualifications - visit 2, n (%)</td><td>1</td><td>1</td><td>5717 (17.6)</td><td>2315 (18.2)</td><td>3402 (17.2)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.060</td></tr><tr><td>0</td><td>0</td><td>31809 (97.9)</td><td>12440 (97.8)</td><td>19369 (97.9)</td></tr><tr><td rowspan="2">Obesity, n (%)</td><td>No</td><td>No</td><td>644 (2.0)</td><td>260 (2.0)</td><td>384 (1.9)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.060</td></tr><tr><td>other</td><td>other</td><td>45 (0.1)</td><td>20 (0.2)</td><td>25 (0.1)</td></tr><tr><td rowspan="2">Past tobacco smoking - visit 2, n (%)</td><td>I have never smoked</td><td>I have never smoked</td><td>15218 (46.8)</td><td>5296 (16.3)</td><td>4008 (12.3)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.060</td></tr><tr><td>Just tried once or twice</td><td>Just tried once or twice</td><td>2008 (15.8)</td><td>1569 (12.3)</td><td>3016 (23.7)</td></tr><tr><td rowspan="2">Qualifications - visit 2, n (%)</td><td>Smoked occasionally</td><td>Smoked on most or all days</td><td>7287 (22.4)</td><td>689 (2.1)</td><td>298 (2.3)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.070</td></tr><tr><td>other</td><td>other</td><td>4013 (12.3)</td><td>1610 (12.7)</td><td>2403 (12.1)</td></tr><tr><td rowspan="2">Obesity, n (%)</td><td>A levels/AS levels or equivalent</td><td>A levels/AS levels or equivalent</td><td>1205 (3.7)</td><td>487 (3.8)</td><td>718 (3.6)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.070</td></tr><tr><td>CSEs or equivalent</td><td>CSEs or equivalent</td><td>16203 (49.9)</td><td>6104 (48.0)</td><td>10099 (51.1)</td></tr><tr><td rowspan="2">Past tobacco smoking - visit 2, n (%)</td><td>College or University degree</td><td>College or University degree</td><td>1901 (5.8)</td><td>778 (6.1)</td><td>1123 (5.7)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.070</td></tr><tr><td>NVQ or HND or HNC or equivalent</td><td>NVQ or HND or HNC or equivalent</td><td>1762 (5.4)</td><td>745 (5.9)</td><td>1017 (5.1)</td></tr><tr><td rowspan="2">Obesity, n (%)</td><td>None of the above</td><td>None of the above</td><td>5717 (17.6)</td><td>2283 (17.9)</td><td>3434 (17.4)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.070</td></tr><tr><td>O levels/GCSEs or equivalent</td><td>O levels/GCSEs or equivalent</td><td>1596 (4.9)</td><td>661 (5.2)</td><td>935 (4.7)</td></tr></tbody></table>
...continued

<table><caption>Table S11: Baseline characteristics of for the included participants, according to their inflammation status. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure being chronic inflammation). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Lack of social support</th><th>Social support</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="12"></td><td>Scanner lateral (x) brain position - visit 2, mean (SD)</td><td rowspan="12">other</td><td>101 (0.3)</td><td>52 (0.4)</td><td>49 (0.2)</td><td rowspan="12">0.757</td><td rowspan="12">Two Sample T-test</td><td rowspan="12">0.004</td></tr><tr><td>Scanner longitudinal (z) brain position - visit 2, mean (SD)</td><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.7 (3.0)</td></tr><tr><td>Scanner table position - visit 2, mean (SD)</td><td>-28.1 (26.8)</td><td>-28.3 (26.8)</td><td>-28.0 (26.7)</td></tr><tr><td>Scanner transverse (y) brain position - visit 2, mean (SD)</td><td>-1054.2 (25.1)</td><td>-1054.4 (25.1)</td><td>-1054.2 (25.1)</td></tr><tr><td>Self declared mental exclude visit 2, mean (SD)</td><td>66.4 (5.9)</td><td>66.5 (5.9)</td><td>66.3 (5.9)</td></tr><tr><td>Sex - visit 0, n (%)</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td></tr><tr><td rowspan="4">Smoking status - visit 2, n (%)</td><td>Female</td><td>17195 (52.9)</td><td>6404 (50.3)</td><td>10791 (54.6)</td><td rowspan="4">&lt;0.001</td><td rowspan="4">Chi-squared</td><td rowspan="4">0.084</td></tr><tr><td>Male</td><td>15303 (47.1)</td><td>6316 (49.7)</td><td>8987 (45.4)</td></tr><tr><td>Current</td><td>1065 (3.3)</td><td>456 (3.6)</td><td>609 (3.1)</td></tr><tr><td>Never</td><td>20503 (63.1)</td><td>7831 (61.6)</td><td>12672 (64.1)</td></tr><tr><td rowspan="2">Total alcohol weekly units 2, mean (SD)</td><td>Previous other</td><td>10846 (33.4)</td><td>4394 (34.5)</td><td>6452 (32.6)</td><td rowspan="2">0.002</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.034</td></tr><tr><td></td><td>84 (0.3)</td><td>39 (0.3)</td><td>45 (0.2)</td></tr><tr><td>Townsend deprivation index at recruitment - visit 0, mean (SD)</td><td></td><td></td><td>13.1 (14.4)</td><td>13.1 (15.0)</td><td>13.1 (14.0)</td><td>0.988</td><td>Two Sample T-test</td><td>-0.000</td></tr><tr><td>Uk biobank assessment centre - visit 2, n (%)</td><td>Cheadle</td><td></td><td>-1.9 (2.7)</td><td>-1.8 (2.8)</td><td>-2.0 (2.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.071</td></tr><tr><td rowspan="3">Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td>Newcastle</td><td></td><td>18991 (58.4)</td><td>7418 (58.3)</td><td>11573 (58.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.069</td></tr><tr><td>Reading other</td><td></td><td>8436 (26.0)</td><td>3146 (24.7)</td><td>5290 (26.7)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>5028 (15.5)</td><td>2139 (16.8)</td><td>2889 (14.6)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>43 (0.1)</td><td>17 (0.1)</td><td>26 (0.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.046</td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No inflammation</th><th>Inflammation</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="12">Sample size<br>Outcome<br>Mediators</td><td>n</td><td></td><td>32498</td><td>27267</td><td>5231</td><td rowspan="12">&lt;0.001</td><td rowspan="12">Two Sample T-test</td><td rowspan="12">0.095</td></tr><tr><td>G factor, mean (SD)</td><td></td><td>-0.0 (1.1)</td><td>-0.1 (1.1)</td><td>0.1 (1.2)</td></tr><tr><td>Dmri pc 0, mean (SD)</td><td></td><td>-0.3 (10.2)</td><td>-0.4 (10.1)</td><td>0.4 (10.5)</td></tr><tr><td>Dmri pc 1, mean (SD)</td><td></td><td>0.1 (5.2)</td><td>0.1 (5.2)</td><td>-0.1 (5.4)</td></tr><tr><td>Dmri pc 2, mean (SD)</td><td></td><td>-0.1 (5.0)</td><td>-0.3 (4.9)</td><td>0.7 (5.8)</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td></td><td>0.0 (4.4)</td><td>-0.1 (4.4)</td><td>0.6 (4.4)</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td></td><td>0.0 (4.2)</td><td>0.0 (4.2)</td><td>0.1 (4.6)</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td></td><td>0.0 (3.4)</td><td>0.0 (3.4)</td><td>-0.2 (3.5)</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td></td><td>-0.4 (10.5)</td><td>-0.6 (10.4)</td><td>0.7 (10.8)</td></tr><tr><td>Smri dmri pc 1, mean (SD)</td><td></td><td>-0.2 (7.4)</td><td>-0.4 (7.4)</td><td>0.8 (7.6)</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td></td><td>0.1 (5.6)</td><td>0.2 (5.5)</td><td>-0.5 (5.7)</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td></td><td>-0.0 (4.7)</td><td>-0.1 (4.5)</td><td>0.4 (5.5)</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td></td><td>-0.0 (4.3)</td><td>-0.1 (4.3)</td><td>0.7 (4.3)</td></tr><tr><td>Smri dmri pc 5, mean (SD)</td><td></td><td>0.0 (4.3)</td><td>0.0 (4.2)</td><td>0.1 (4.5)</td></tr><tr><td>Smri pc 0, mean (SD)</td><td></td><td>0.3 (7.2)</td><td>0.5 (7.1)</td><td>-0.9 (7.2)</td><td rowspan="4">&lt;0.001</td><td rowspan="4">Two Sample T-test</td><td rowspan="4">0.159</td></tr><tr><td>Smri pc 1, mean (SD)</td><td></td><td>-0.0 (3.3)</td><td>-0.1 (3.3)</td><td>0.4 (3.3)</td></tr><tr><td>Smri pc 2, mean (SD)</td><td></td><td>-0.1 (2.8)</td><td>-0.1 (2.8)</td><td>-0.1 (2.9)</td></tr><tr><td>Smri pc 3, mean (SD)</td><td></td><td>0.0 (2.1)</td><td>-0.0 (2.1)</td><td>0.0 (2.0)</td></tr><tr><td rowspan="4">Confounders (alphabetic order)</td><td>Adopted as a child - visit 0, n (%)</td><td>No</td><td>32469 (99.9)</td><td>27244 (99.9)</td><td>5225 (99.9)</td><td>0.512</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.016</td></tr><tr><td rowspan="2">Age when attended assessment centre - visit 2, mean (SD)</td><td>Yes</td><td>9 (0.0)</td><td>8 (0.0)</td><td>1 (0.0)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">0.076</td></tr><tr><td>other</td><td>20 (0.1)</td><td>15 (0.1)</td><td>5 (0.1)</td></tr><tr><td>Alcohol above nhs reco, n (%)</td><td>0</td><td>63.7 (7.6)</td><td>63.6 (7.6)</td><td>64.2 (7.6)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>1</td><td>21256 (65.4)</td><td>17639 (64.7)</td><td>3617 (69.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>11242 (34.6)</td><td>9628 (35.3)</td><td>1614 (30.9)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.095</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No inflammation</th><th>Inflammation</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10"></td><td rowspan="10">Alcohol intake frequency - visit 2, n (%)</td><td>Daily or almost daily</td><td>5540 (17.0)</td><td>4788 (17.6)</td><td>752 (14.4)</td><td rowspan="10">&lt;0.001</td><td rowspan="10">Chi-squared</td><td rowspan="10">0.214</td></tr><tr><td>Never</td><td>2032 (6.3)</td><td>1612 (5.9)</td><td>420 (8.0)</td></tr><tr><td>Once or twice a week</td><td>8640 (26.6)</td><td>7287 (26.7)</td><td>1353 (25.9)</td></tr><tr><td>One to three times a month</td><td>3788 (11.7)</td><td>3068 (11.3)</td><td>720 (13.8)</td></tr><tr><td>Special occasions only</td><td>3262 (10.0)</td><td>2539 (9.3)</td><td>723 (13.8)</td></tr><tr><td>Three or four times a week</td><td>9236 (28.4)</td><td>7973 (29.2)</td><td>1263 (24.1)</td></tr><tr><td>18,000 to 30,999</td><td>7813 (24.0)</td><td>6436 (23.6)</td><td>1377 (26.3)</td></tr><tr><td>31,000 to 51,999</td><td>9156 (28.2)</td><td>7729 (28.3)</td><td>1427 (27.3)</td></tr><tr><td>52,000 to 100,000</td><td>7028 (21.6)</td><td>6066 (22.2)</td><td>962 (18.4)</td></tr><tr><td>Do not know</td><td>961 (3.0)</td><td>773 (2.8)</td><td>188 (3.6)</td></tr><tr><td>Greater than 100,000</td><td>2277 (7.0)</td><td>1983 (7.3)</td><td>294 (5.6)</td></tr><tr><td>Less than 18,000</td><td>3402 (10.5)</td><td>2724 (10.0)</td><td>678 (13.0)</td></tr><tr><td>Prefer not to answer</td><td>1861 (5.7)</td><td>1556 (5.7)</td><td>305 (5.8)</td></tr><tr><td>Body mass index (bmi) - visit 2, mean (SD)</td><td></td><td></td><td>26.4 (4.3)</td><td>25.9 (3.9)</td><td>29.2 (5.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.704</td></tr><tr><td rowspan="5">Breastfed as a baby - visit 0, n (%)</td><td>Do not know</td><td>6175 (19.0)</td><td>5123 (18.8)</td><td>1052 (20.1)</td><td>0.022</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.047</td></tr><tr><td>No</td><td>7174 (22.1)</td><td>5978 (21.9)</td><td>1196 (22.9)</td><td rowspan="5">&lt;0.001</td><td rowspan="5">Chi-squared</td><td rowspan="5">0.058</td></tr><tr><td>Yes</td><td>19136 (58.9)</td><td>16155 (59.2)</td><td>2981 (57.0)</td></tr><tr><td>other</td><td>13 (0.0)</td><td>11 (0.0)</td><td>2 (0.0)</td></tr><tr><td>False</td><td>23413 (72.0)</td><td>19760 (72.5)</td><td>3653 (69.8)</td></tr><tr><td>True</td><td>9085 (28.0)</td><td>7507 (27.5)</td><td>1578 (30.2)</td></tr><tr><td>Comparative body size at age 10 - visit 0, n (%)</td><td>About average</td><td>16637 (51.2)</td><td>14129 (51.8)</td><td>2508 (47.9)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.151</td></tr><tr><td rowspan="5">Comparative height size at age 10 - visit 0, n (%)</td><td>Do not know</td><td>347 (1.1)</td><td>283 (1.0)</td><td>64 (1.2)</td><td rowspan="5">0.766</td><td rowspan="5">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="5">0.020</td></tr><tr><td>Plumper</td><td>4922 (15.1)</td><td>3886 (14.3)</td><td>1036 (19.8)</td></tr><tr><td>Thinner</td><td>10584 (32.6)</td><td>8963 (32.9)</td><td>1621 (31.0)</td></tr><tr><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.0)</td></tr><tr><td>About average</td><td>17039 (52.4)</td><td>14279 (52.4)</td><td>2760 (52.8)</td></tr><tr><td rowspan="5">Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>Do not know</td><td>293 (0.9)</td><td>240 (0.9)</td><td>53 (1.0)</td><td rowspan="5">0.043</td><td rowspan="5">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="5">0.051</td></tr><tr><td>Shorter</td><td>6569 (20.2)</td><td>5515 (20.2)</td><td>1054 (20.1)</td></tr><tr><td>Taller</td><td>8589 (26.4)</td><td>7227 (26.5)</td><td>1362 (26.0)</td></tr><tr><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.0)</td></tr><tr><td>Elsewhere</td><td>1778 (5.5)</td><td>1520 (5.6)</td><td>258 (4.9)</td></tr><tr><td rowspan="10"></td><td rowspan="10">Current employment status - visit 2, n (%)</td><td>England</td><td>27360 (84.2)</td><td>22911 (84.0)</td><td>4449 (85.1)</td><td rowspan="10">&lt;0.001</td><td rowspan="10">Chi-squared</td><td rowspan="10">0.073</td></tr><tr><td>Northern Ireland</td><td>234 (0.7)</td><td>202 (0.7)</td><td>32 (0.6)</td></tr><tr><td>Republic of Ireland</td><td>217 (0.7)</td><td>182 (0.7)</td><td>35 (0.7)</td></tr><tr><td>Scotland</td><td>2296 (7.1)</td><td>1951 (7.2)</td><td>345 (6.6)</td></tr><tr><td>Wales</td><td>600 (1.8)</td><td>493 (1.8)</td><td>107 (2.0)</td></tr><tr><td>other</td><td>13 (0.0)</td><td>8 (0.0)</td><td>5 (0.1)</td></tr><tr><td>In paid employment or self-employed</td><td>12978 (39.9)</td><td>11037 (40.5)</td><td>1941 (37.1)</td></tr><tr><td>Retired</td><td>18302 (56.3)</td><td>15237 (55.9)</td><td>3065 (58.6)</td></tr><tr><td>other</td><td>1218 (3.7)</td><td>993 (3.6)</td><td>225 (4.3)</td></tr><tr><td>Current smoker, n (%)</td><td>0</td><td>31893 (98.1)</td><td>26820 (98.4)</td><td>5073 (97.0)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.092</td></tr><tr><td>1</td><td>605 (1.9)</td><td>447 (1.6)</td><td>158 (3.0)</td></tr><tr><td rowspan="3">Current tobacco smoking - visit 2, n (%)</td><td>No</td><td>31431 (96.7)</td><td>26428 (96.9)</td><td>5003 (95.6)</td><td rowspan="3">&lt;0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.092</td></tr><tr><td>Yes, on most or all days</td><td>605 (1.9)</td><td>447 (1.6)</td><td>158 (3.0)</td></tr><tr><td>other</td><td>462 (1.4)</td><td>392 (1.4)</td><td>70 (1.3)</td></tr><tr><td rowspan="2">Diabetic, n (%)</td><td>0</td><td>31154 (95.9)</td><td>26325 (96.5)</td><td>4829 (92.3)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.185</td></tr><tr><td>1</td><td>1344 (4.1)</td><td>942 (3.5)</td><td>402 (7.7)</td></tr><tr><td rowspan="3">Ethnic background - visit 2, n (%)</td><td>British</td><td>7408 (22.8)</td><td>6120 (22.4)</td><td>1288 (24.6)</td><td rowspan="3">0.001</td><td rowspan="3">Chi-squared</td><td rowspan="3">0.051</td></tr><tr><td>other</td><td>25090 (77.2)</td><td>21147 (77.6)</td><td>3943 (75.4)</td></tr><tr><td>No</td><td>15217 (46.8)</td><td>12905 (47.3)</td><td>2312 (44.2)</td></tr><tr><td rowspan="2">Ever smoked - visit 2, n (%)</td><td>Yes</td><td>17196 (52.9)</td><td>14297 (52.4)</td><td>2899 (55.4)</td><td rowspan="2">&lt;0.001</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.067</td></tr><tr><td>other</td><td>85 (0.3)</td><td>65 (0.2)</td><td>20 (0.4)</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No inflammation</th><th>Inflammation</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td></td><td>Handedness (chirality/laterality) - visit 0, n (%)</td><td>Left-handed</td><td>3043 (9.4)</td><td>2560 (9.4)</td><td>483 (9.2)</td><td>0.842</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.013</td></tr><tr><td></td><td></td><td>Right-handed</td><td>28957 (89.1)</td><td>24291 (89.1)</td><td>4666 (89.2)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Use both right and left hands equally</td><td>486 (1.5)</td><td>407 (1.5)</td><td>79 (1.5)</td><td></td><td></td><td></td></tr><tr><td></td><td>Hypercholesterol, n (%)</td><td>other</td><td>12 (0.0)</td><td>9 (0.0)</td><td>3 (0.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>0</td><td>24538 (75.5)</td><td>20848 (76.5)</td><td>3690 (70.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.134</td></tr><tr><td></td><td></td><td>1</td><td>7960 (24.5)</td><td>6419 (23.5)</td><td>1541 (29.5)</td><td></td><td></td><td></td></tr><tr><td></td><td>Hypertensive, n (%)</td><td>0</td><td>23962 (73.7)</td><td>20553 (75.4)</td><td>3409 (65.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.225</td></tr><tr><td></td><td></td><td>1</td><td>8536 (26.3)</td><td>6714 (24.6)</td><td>1822 (34.8)</td><td></td><td></td><td></td></tr><tr><td></td><td>Job involves shift work - visit 2, n (%)</td><td>Always</td><td>795 (2.4)</td><td>653 (2.4)</td><td>142 (2.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.079</td></tr><tr><td></td><td></td><td>Never/rarely</td><td>11077 (34.1)</td><td>9453 (34.7)</td><td>1624 (31.0)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Sometimes</td><td>855 (2.6)</td><td>720 (2.6)</td><td>135 (2.6)</td><td></td><td></td><td></td></tr><tr><td></td><td>Length of time at current address - visit 2, mean (SD)</td><td>other</td><td>19771 (60.8)</td><td>16441 (60.3)</td><td>3330 (63.7)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>21.0 (13.9)</td><td>21.0 (13.8)</td><td>21.2 (14.2)</td><td>0.427</td><td>Two Sample T-test</td><td>0.012</td></tr><tr><td></td><td>Life long depression, n (%)</td><td>False</td><td>27461 (84.5)</td><td>23161 (84.9)</td><td>4300 (82.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.074</td></tr><tr><td></td><td></td><td>True</td><td>5037 (15.5)</td><td>4106 (15.1)</td><td>931 (17.8)</td><td></td><td></td><td></td></tr><tr><td></td><td>Ls pc dim.1, mean (SD)</td><td></td><td>0.6 (2.0)</td><td>0.7 (2.0)</td><td>0.1 (2.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.292</td></tr><tr><td></td><td>Ls pc dim.2, mean (SD)</td><td></td><td>-0.4 (2.0)</td><td>-0.4 (2.0)</td><td>-0.6 (2.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.090</td></tr><tr><td></td><td>Maternal smoking around birth - visit 0, n (%)</td><td>Do not know</td><td>3388 (10.4)</td><td>2825 (10.4)</td><td>563 (10.8)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.065</td></tr><tr><td></td><td></td><td>No</td><td>20344 (62.6)</td><td>17203 (63.1)</td><td>3141 (60.0)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Yes</td><td>8749 (26.9)</td><td>7225 (26.5)</td><td>1524 (29.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>17 (0.1)</td><td>14 (0.1)</td><td>3 (0.1)</td><td></td><td></td><td></td></tr><tr><td></td><td>Mh pc dim.1, mean (SD)</td><td></td><td>1.0 (6.5)</td><td>1.1 (6.5)</td><td>0.4 (6.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.116</td></tr><tr><td></td><td>Mh pc dim.2, mean (SD)</td><td></td><td>0.5 (3.3)</td><td>0.5 (3.3)</td><td>0.2 (3.4)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.098</td></tr><tr><td></td><td>Number in household - visit 2, mean (SD)</td><td></td><td>2.2 (1.0)</td><td>2.2 (1.0)</td><td>2.1 (1.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.068</td></tr><tr><td></td><td>Number of full brothers - visit 2, mean (SD)</td><td></td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.1 (1.2)</td><td>0.017</td><td>Two Sample T-test</td><td>0.036</td></tr><tr><td></td><td>Number of full sisters - visit 2, mean (SD)</td><td></td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>0.005</td><td>Two Sample T-test</td><td>0.043</td></tr><tr><td></td><td>Number of vehicles in household - visit 2, n (%)</td><td>Four or more</td><td>922 (2.8)</td><td>781 (2.9)</td><td>141 (2.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.090</td></tr><tr><td></td><td></td><td>None</td><td>1265 (3.9)</td><td>1016 (3.7)</td><td>249 (4.8)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>One</td><td>13770 (42.4)</td><td>11434 (41.9)</td><td>2336 (44.7)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Three</td><td>3034 (9.3)</td><td>2595 (9.5)</td><td>439 (8.4)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Two</td><td>13471 (41.5)</td><td>11407 (41.8)</td><td>2064 (39.5)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>36 (0.1)</td><td>34 (0.1)</td><td>2 (0.0)</td><td></td><td></td><td></td></tr><tr><td></td><td>Obesity, n (%)</td><td>0</td><td>26781 (82.4)</td><td>23527 (86.3)</td><td>3254 (62.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.573</td></tr><tr><td></td><td></td><td>1</td><td>5717 (17.6)</td><td>3740 (13.7)</td><td>1977 (37.8)</td><td></td><td></td><td></td></tr><tr><td></td><td>Part of a multiple birth - visit 0, n (%)</td><td>No</td><td>31809 (97.9)</td><td>26684 (97.9)</td><td>5125 (98.0)</td><td>0.791</td><td>Chi-squared</td><td>0.010</td></tr><tr><td></td><td></td><td>Yes</td><td>644 (2.0)</td><td>546 (2.0)</td><td>98 (1.9)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>45 (0.1)</td><td>37 (0.1)</td><td>8 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Past tobacco smoking - visit 2, n (%)</td><td>I have never smoked</td><td>15218 (46.8)</td><td>12906 (47.3)</td><td>2312 (44.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.175</td></tr><tr><td></td><td></td><td>Just tried once or twice</td><td>5296 (16.3)</td><td>4569 (16.8)</td><td>727 (13.9)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Smoked occasionally</td><td>4008 (12.3)</td><td>3413 (12.5)</td><td>595 (11.4)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Smoked on most or all days</td><td>7287 (22.4)</td><td>5868 (21.5)</td><td>1419 (27.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>689 (2.1)</td><td>511 (1.9)</td><td>178 (3.4)</td><td></td><td></td><td></td></tr><tr><td></td><td>Qualifications - visit 2, n (%)</td><td>A levels/AS levels or equivalent</td><td>4013 (12.3)</td><td>3358 (12.3)</td><td>655 (12.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.182</td></tr><tr><td></td><td></td><td>CSEs or equivalent</td><td>1205 (3.7)</td><td>990 (3.6)</td><td>215 (4.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>College or University degree</td><td>16203 (49.9)</td><td>13951 (51.2)</td><td>2252 (43.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>NVQ or HND or HNC or equivalent</td><td>1901 (5.8)</td><td>1578 (5.8)</td><td>323 (6.2)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>None of the above</td><td>1762 (5.4)</td><td>1372 (5.0)</td><td>390 (7.5)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>O levels/GCSEs or equivalent</td><td>5717 (17.6)</td><td>4639 (17.0)</td><td>1078 (20.6)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Other professional qualifications eg: nursing, teaching other</td><td>1596 (4.9)</td><td>1296 (4.8)</td><td>300 (5.7)</td><td></td><td></td><td></td></tr><tr><td></td><td>Scanner lateral (x) brain position - visit 2, mean (SD)</td><td></td><td>101 (0.3)</td><td>83 (0.3)</td><td>18 (0.3)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.257</td><td>Two Sample T-test</td><td>-0.017</td></tr></tbody></table>
...continued

<table><caption>Table S12: Baseline characteristics of for the included participants, according to their current smoker status. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure being current smoking). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No inflammation</th><th>Inflammation</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10"></td><td>Scanner longitudinal (z) brain position - visit 2, mean (SD)</td><td rowspan="10"></td><td>-28.1 (26.8)</td><td>-27.8 (26.6)</td><td>-29.5 (27.5)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.064</td></tr><tr><td>Scanner table position - visit 2, mean (SD)</td><td>-1054.2 (25.1)</td><td>-1054.1 (24.9)</td><td>-1055.1 (25.9)</td><td>0.012</td><td>Two Sample T-test</td><td>-0.038</td></tr><tr><td>Scanner transverse (y) brain position - visit 2, mean (SD)</td><td>66.4 (5.9)</td><td>66.3 (5.9)</td><td>66.6 (6.1)</td><td>0.016</td><td>Two Sample T-test</td><td>0.037</td></tr><tr><td>Self declared mental exclusion visit 2, mean (SD)</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.093</td><td>Two Sample T-test</td><td>0.026</td></tr><tr><td>Sex - visit 0, n (%)</td><td>Female</td><td>17195 (52.9)</td><td>14154 (51.9)</td><td>3041 (58.1)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.125</td></tr><tr><td>Smoking status - visit 2, n (%)</td><td>Male</td><td>15303 (47.1)</td><td>13113 (48.1)</td><td>2190 (41.9)</td><td></td><td></td><td></td></tr><tr><td></td><td>Current</td><td>1065 (3.3)</td><td>837 (3.1)</td><td>228 (4.4)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.130</td></tr><tr><td></td><td>Never</td><td>20503 (63.1)</td><td>17464 (64.0)</td><td>3039 (58.1)</td><td></td><td></td><td></td></tr><tr><td></td><td>Previous other</td><td>10846 (33.4)</td><td>8902 (32.6)</td><td>1944 (37.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Social support, n (%)</td><td>False</td><td>84 (0.3)</td><td>64 (0.2)</td><td>20 (0.4)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>True</td><td>12720 (39.1)</td><td>10565 (38.7)</td><td>2155 (41.2)</td><td>0.001</td><td>Chi-squared</td><td>0.050</td></tr><tr><td></td><td>Total alcohol weekly units 2, mean (SD)</td><td rowspan="3">Cheadle</td><td>19778 (60.9)</td><td>16702 (61.3)</td><td>3076 (58.8)</td><td></td><td></td><td></td></tr><tr><td></td><td>Townsend deprivation index at recruitment - visit 0, mean (SD)</td><td>13.1 (14.4)</td><td>13.3 (14.4)</td><td>12.1 (14.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.086</td></tr><tr><td></td><td>Uk biobank assessment centre - visit 2, n (%)</td><td>-1.9 (2.7)</td><td>-2.0 (2.7)</td><td>-1.7 (2.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.097</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td>Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td>Newcastle</td><td>18991 (58.4)</td><td>15829 (58.1)</td><td>3162 (60.4)</td><td>0.013</td><td>Chi-squared</td><td>0.050</td></tr><tr><td></td><td></td><td>Reading other</td><td>8436 (26.0)</td><td>7132 (26.2)</td><td>1304 (24.9)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>5028 (15.5)</td><td>4269 (15.7)</td><td>759 (14.5)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>43 (0.1)</td><td>37 (0.1)</td><td>6 (0.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.121</td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No current smoking</th><th>Current smoking</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10">Sample size<br>Outcome<br>Mediators</td><td>n</td><td></td><td>32498</td><td>31893</td><td>605</td><td></td><td></td><td></td></tr><tr><td>G factor, mean (SD)</td><td></td><td>-0.0 (1.1)</td><td>-0.0 (1.1)</td><td>0.1 (1.1)</td><td>0.006</td><td>Two Sample T-test</td><td>0.114</td></tr><tr><td>Dmri pc 0, mean (SD)</td><td></td><td>-0.3 (10.2)</td><td>-0.3 (10.2)</td><td>0.7 (10.6)</td><td>0.026</td><td>Two Sample T-test</td><td>0.093</td></tr><tr><td>Dmri pc 1, mean (SD)</td><td></td><td>0.1 (5.2)</td><td>0.1 (5.2)</td><td>0.3 (5.1)</td><td>0.278</td><td>Two Sample T-test</td><td>0.044</td></tr><tr><td>Dmri pc 2, mean (SD)</td><td></td><td>-0.1 (5.0)</td><td>-0.1 (5.0)</td><td>-0.1 (4.5)</td><td>0.890</td><td>Two Sample T-test</td><td>0.005</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td></td><td>0.0 (4.4)</td><td>-0.0 (4.4)</td><td>0.8 (4.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.195</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td></td><td>0.0 (4.2)</td><td>0.0 (4.2)</td><td>0.2 (4.2)</td><td>0.189</td><td>Two Sample T-test</td><td>0.054</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td></td><td>0.0 (3.4)</td><td>0.0 (3.4)</td><td>-0.2 (3.5)</td><td>0.154</td><td>Two Sample T-test</td><td>-0.059</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td></td><td>-0.4 (10.5)</td><td>-0.4 (10.5)</td><td>0.5 (10.9)</td><td>0.062</td><td>Two Sample T-test</td><td>0.078</td></tr><tr><td>Smri dmri pc 1, mean (SD)</td><td></td><td>-0.2 (7.4)</td><td>-0.2 (7.4)</td><td>-0.7 (7.5)</td><td>0.093</td><td>Two Sample T-test</td><td>-0.069</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td></td><td>0.1 (5.6)</td><td>0.1 (5.6)</td><td>0.5 (5.4)</td><td>0.136</td><td>Two Sample T-test</td><td>0.060</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td></td><td>-0.0 (4.7)</td><td>-0.0 (4.7)</td><td>0.4 (4.2)</td><td>0.012</td><td>Two Sample T-test</td><td>0.097</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td></td><td>-0.0 (4.3)</td><td>-0.0 (4.3)</td><td>0.7 (3.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.176</td></tr><tr><td>Smri dmri pc 5, mean (SD)</td><td></td><td>0.0 (4.3)</td><td>0.0 (4.3)</td><td>0.3 (4.3)</td><td>0.145</td><td>Two Sample T-test</td><td>0.060</td></tr><tr><td>Smri pc 0, mean (SD)</td><td></td><td>0.3 (7.2)</td><td>0.3 (7.2)</td><td>0.5 (7.3)</td><td>0.341</td><td>Two Sample T-test</td><td>0.039</td></tr><tr><td>Smri pc 1, mean (SD)</td><td></td><td>-0.0 (3.3)</td><td>-0.0 (3.3)</td><td>0.3 (3.3)</td><td>0.026</td><td>Two Sample T-test</td><td>0.091</td></tr><tr><td>Smri pc 2, mean (SD)</td><td></td><td>-0.1 (2.8)</td><td>-0.1 (2.8)</td><td>-0.3 (2.9)</td><td>0.094</td><td>Two Sample T-test</td><td>-0.070</td></tr><tr><td>Smri pc 3, mean (SD)</td><td></td><td>0.0 (2.1)</td><td>-0.0 (2.1)</td><td>0.3 (2.1)</td><td>0.001</td><td>Two Sample T-test</td><td>0.137</td></tr><tr><td rowspan="5">Confounders (alphabetic order)</td><td>Adopted as a child - visit 0, n (%)</td><td>No</td><td>32469 (99.9)</td><td>31867 (99.9)</td><td>602 (99.5)</td><td>0.003</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.077</td></tr><tr><td></td><td>Yes</td><td>9 (0.0)</td><td>8 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>other</td><td>20 (0.1)</td><td>18 (0.1)</td><td>2 (0.3)</td><td></td><td></td><td></td></tr><tr><td>Age when attended assessment centre - visit 2, mean (SD)</td><td></td><td>63.7 (7.6)</td><td>63.8 (7.6)</td><td>60.9 (7.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.377</td></tr><tr><td>Alcohol above nhs reco, n (%)</td><td>0</td><td>21256 (65.4)</td><td>20926 (65.6)</td><td>330 (54.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.227</td></tr><tr><td rowspan="2"></td><td rowspan="2">Alcohol intake frequency. - visit 2, n (%)</td><td>Daily or almost daily</td><td>11242 (34.6)</td><td>10967 (34.4)</td><td>275 (45.5)</td><td></td><td></td><td></td></tr><tr><td>Never</td><td>5540 (17.0)</td><td>5380 (16.9)</td><td>160 (26.4)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.333</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No current smoking</th><th>Current smoking</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10">Average total household income before tax - visit 2, n (%)</td><td rowspan="10">Average total household income before tax - visit 2, n (%)</td><td>Once or twice a week</td><td>8640 (26.6)</td><td>8499 (26.6)</td><td>141 (23.3)</td><td></td><td></td><td></td></tr><tr><td>One to three times a month</td><td>3788 (11.7)</td><td>3713 (11.6)</td><td>75 (12.4)</td><td></td><td></td><td></td></tr><tr><td>Special occasions only</td><td>3262 (10.0)</td><td>3184 (10.0)</td><td>78 (12.9)</td><td></td><td></td><td></td></tr><tr><td>Three or four times a week</td><td>9236 (28.4)</td><td>9129 (28.6)</td><td>107 (17.7)</td><td></td><td></td><td></td></tr><tr><td>18,000 to 30,999</td><td>7813 (24.0)</td><td>7654 (24.0)</td><td>159 (26.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.275</td></tr><tr><td>31,000 to 51,999</td><td>9156 (28.2)</td><td>9010 (28.3)</td><td>146 (24.1)</td><td></td><td></td><td></td></tr><tr><td>52,000 to 100,000</td><td>7028 (21.6)</td><td>6923 (21.7)</td><td>105 (17.4)</td><td></td><td></td><td></td></tr><tr><td>Do not know</td><td>961 (3.0)</td><td>944 (3.0)</td><td>17 (2.8)</td><td></td><td></td><td></td></tr><tr><td>Greater than 100,000</td><td>2277 (7.0)</td><td>2249 (7.1)</td><td>28 (4.6)</td><td></td><td></td><td></td></tr><tr><td>Less than 18,000</td><td>3402 (10.5)</td><td>3291 (10.3)</td><td>111 (18.3)</td><td></td><td></td><td></td></tr><tr><td>Prefer not to answer</td><td>1861 (5.7)</td><td>1822 (5.7)</td><td>39 (6.4)</td><td></td><td></td><td></td></tr><tr><td>Body mass index (bmi) - visit 2, mean (SD)</td><td>Body mass index (bmi) - visit 2, mean (SD)</td><td>Do not know</td><td>6175 (19.0)</td><td>6051 (19.0)</td><td>124 (20.5)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.018</td></tr><tr><td rowspan="4">Breastfed as a baby - visit 0, n (%)</td><td rowspan="4">Breastfed as a baby - visit 0, n (%)</td><td>No</td><td>7174 (22.1)</td><td>7019 (22.0)</td><td>155 (25.6)</td><td></td><td></td><td></td></tr><tr><td>Yes</td><td>19136 (58.9)</td><td>18812 (59.0)</td><td>324 (53.6)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>13 (0.0)</td><td>11 (0.0)</td><td>2 (0.3)</td><td></td><td></td><td></td></tr><tr><td>False</td><td>23413 (72.0)</td><td>23036 (72.2)</td><td>377 (62.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.212</td></tr><tr><td rowspan="2">Cmdd final, n (%)</td><td rowspan="2">Cmdd final, n (%)</td><td>True</td><td>9085 (28.0)</td><td>8857 (27.8)</td><td>228 (37.7)</td><td></td><td></td><td></td></tr><tr><td>About average</td><td>16637 (51.2)</td><td>16334 (51.2)</td><td>303 (50.1)</td><td>0.036</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.103</td></tr><tr><td rowspan="4">Comparative body size at age 10 - visit 0, n (%)</td><td rowspan="4">Comparative body size at age 10 - visit 0, n (%)</td><td>Do not know</td><td>347 (1.1)</td><td>339 (1.1)</td><td>8 (1.3)</td><td></td><td></td><td></td></tr><tr><td>Plumper</td><td>4922 (15.1)</td><td>4812 (15.1)</td><td>110 (18.2)</td><td></td><td></td><td></td></tr><tr><td>Thinner</td><td>10584 (32.6)</td><td>10401 (32.6)</td><td>183 (30.2)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>8 (0.0)</td><td>7 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Comparative height size at age 10 - visit 0, n (%)</td><td rowspan="2">Comparative height size at age 10 - visit 0, n (%)</td><td>About average</td><td>17039 (52.4)</td><td>16739 (52.5)</td><td>300 (49.6)</td><td>0.052</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.093</td></tr><tr><td>Do not know</td><td>293 (0.9)</td><td>284 (0.9)</td><td>9 (1.5)</td><td></td><td></td><td></td></tr><tr><td rowspan="4">Country of birth (uk/elsewhere) - visit 0, n (%)</td><td rowspan="4">Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>Shorter</td><td>6569 (20.2)</td><td>6435 (20.2)</td><td>134 (22.1)</td><td></td><td></td><td></td></tr><tr><td>Taller</td><td>8589 (26.4)</td><td>8428 (26.4)</td><td>161 (26.6)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>8 (0.0)</td><td>7 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td>Elsewhere</td><td>1778 (5.5)</td><td>1749 (5.5)</td><td>29 (4.8)</td><td>0.531</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.075</td></tr><tr><td rowspan="10">Current employment status - visit 2, n (%)</td><td rowspan="10">Current employment status - visit 2, n (%)</td><td>England</td><td>27360 (84.2)</td><td>26852 (84.2)</td><td>508 (84.0)</td><td></td><td></td><td></td></tr><tr><td>Northern Ireland</td><td>234 (0.7)</td><td>227 (0.7)</td><td>7 (1.2)</td><td></td><td></td><td></td></tr><tr><td>Republic of Ireland</td><td>217 (0.7)</td><td>214 (0.7)</td><td>3 (0.5)</td><td></td><td></td><td></td></tr><tr><td>Scotland</td><td>2296 (7.1)</td><td>2250 (7.1)</td><td>46 (7.6)</td><td></td><td></td><td></td></tr><tr><td>Wales</td><td>600 (1.8)</td><td>589 (1.8)</td><td>11 (1.8)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>13 (0.0)</td><td>12 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td>In paid employment or self-employed</td><td>12978 (39.9)</td><td>12655 (39.7)</td><td>323 (53.4)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.361</td></tr><tr><td>Retired</td><td>18302 (56.3)</td><td>18064 (56.6)</td><td>238 (39.3)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>1218 (3.7)</td><td>1174 (3.7)</td><td>44 (7.3)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Diabetic, n (%)</td><td rowspan="3">Diabetic, n (%)</td><td>0</td><td>31154 (95.9)</td><td>30589 (95.9)</td><td>565 (93.4)</td><td>0.003</td><td>Chi-squared</td><td>0.112</td></tr><tr><td>1</td><td>1344 (4.1)</td><td>1304 (4.1)</td><td>40 (6.6)</td><td></td><td></td><td></td></tr><tr><td>British</td><td>7408 (22.8)</td><td>7240 (22.7)</td><td>168 (27.8)</td><td>0.004</td><td>Chi-squared</td><td>0.117</td></tr><tr><td rowspan="2">Ethnic background - visit 2, n (%)</td><td rowspan="2">Ethnic background - visit 2, n (%)</td><td>other</td><td>25090 (77.2)</td><td>24653 (77.3)</td><td>437 (72.2)</td><td></td><td></td><td></td></tr><tr><td>Left-handed</td><td>3043 (9.4)</td><td>2984 (9.4)</td><td>59 (9.8)</td><td>0.195</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.067</td></tr><tr><td rowspan="4">Handedness (chirality/laterality) - visit 0, n (%)</td><td rowspan="4">Handedness (chirality/laterality) - visit 0, n (%)</td><td>Right-handed</td><td>28957 (89.1)</td><td>28425 (89.1)</td><td>532 (87.9)</td><td></td><td></td><td></td></tr><tr><td>Use both right and left hands equally</td><td>486 (1.5)</td><td>473 (1.5)</td><td>13 (2.1)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>12 (0.0)</td><td>11 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td>Hypercholesterol, n (%)</td><td>0</td><td>24538 (75.5)</td><td>24089 (75.5)</td><td>449 (74.2)</td><td>0.485</td><td>Chi-squared</td><td>0.030</td></tr><tr><td rowspan="2">Hypertensive, n (%)</td><td rowspan="2">Hypertensive, n (%)</td><td>1</td><td>7960 (24.5)</td><td>7804 (24.5)</td><td>156 (25.8)</td><td></td><td></td><td></td></tr><tr><td>0</td><td>23962 (73.7)</td><td>23497 (73.7)</td><td>465 (76.9)</td><td>0.086</td><td>Chi-squared</td><td>0.074</td></tr><tr><td></td><td></td><td>1</td><td>8536 (26.3)</td><td>8396 (26.3)</td><td>140 (23.1)</td><td></td><td></td><td></td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No current smoking</th><th>Current smoking</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10"></td><td>Inflammation, n (%)</td><td>False</td><td>27267 (83.9)</td><td>26820 (84.1)</td><td>447 (73.9)</td><td rowspan="10">&lt;0.001</td><td>Chi-squared</td><td>0.253</td></tr><tr><td rowspan="4">Job involves shift work - visit 2, n (%)</td><td>True</td><td>5231 (16.1)</td><td>5073 (15.9)</td><td>158 (26.1)</td><td rowspan="4">Chi-squared</td><td rowspan="4">0.291</td></tr><tr><td>Always</td><td>795 (2.4)</td><td>762 (2.4)</td><td>33 (5.5)</td></tr><tr><td>Never/rarely</td><td>11077 (34.1)</td><td>10829 (34.0)</td><td>248 (41.0)</td></tr><tr><td>Sometimes other</td><td>855 (2.6)</td><td>824 (2.6)</td><td>31 (5.1)</td></tr><tr><td rowspan="2">Length of time at current address - visit 2, mean (SD)</td><td>False</td><td>19771 (60.8)</td><td>19478 (61.1)</td><td>293 (48.4)</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.251</td></tr><tr><td>True</td><td>21.0 (13.9)</td><td>21.1 (13.9)</td><td>17.7 (13.3)</td></tr><tr><td>Life long depression, n (%)</td><td>False</td><td>27461 (84.5)</td><td>26982 (84.6)</td><td>479 (79.2)</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.141</td></tr><tr><td>Ls pc dim.1, mean (SD)</td><td>True</td><td>5037 (15.5)</td><td>4911 (15.4)</td><td>126 (20.8)</td></tr><tr><td>Ls pc dim.2, mean (SD)</td><td>False</td><td>0.6 (2.0)</td><td>0.6 (2.0)</td><td>0.2 (2.3)</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.183</td></tr><tr><td>Maternal smoking around birth - visit 0, n (%)</td><td>Do not know</td><td>-0.4 (2.0)</td><td>-0.4 (2.0)</td><td>-1.2 (2.2)</td></tr><tr><td rowspan="2">Mh pc dim.1, mean (SD)</td><td>No</td><td>20344 (62.6)</td><td>20031 (62.8)</td><td>313 (51.7)</td><td rowspan="2">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="2">-0.419</td></tr><tr><td>Yes other</td><td>8749 (26.9)</td><td>8554 (26.8)</td><td>195 (32.2)</td></tr><tr><td>Mh pc dim.2, mean (SD)</td><td>False</td><td>17 (0.1)</td><td>15 (0.0)</td><td>2 (0.3)</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.178</td></tr><tr><td>Number in household - visit 2, mean (SD)</td><td>True</td><td>1.0 (6.5)</td><td>1.1 (6.5)</td><td>-1.8 (7.2)</td></tr><tr><td>Number of full brothers - visit 2, mean (SD)</td><td>False</td><td>0.5 (3.3)</td><td>0.5 (3.3)</td><td>-0.2 (3.6)</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.097</td></tr><tr><td>Number of full sisters - visit 2, mean (SD)</td><td>True</td><td>2.2 (1.0)</td><td>2.2 (1.0)</td><td>2.0 (1.2)</td></tr><tr><td>Number of vehicles in household - visit 2, n (%)</td><td>Four or more</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.2 (1.2)</td><td>Two Sample T-test</td><td>0.133</td></tr><tr><td rowspan="2">Obesity, n (%)</td><td>None</td><td>1265 (3.9)</td><td>1217 (3.8)</td><td>48 (7.9)</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.020</td></tr><tr><td>One Three Two other</td><td>13770 (42.4)</td><td>13502 (42.3)</td><td>268 (44.3)</td></tr><tr><td rowspan="2">Part of a multiple birth - visit 0, n (%)</td><td>0</td><td>3034 (9.3)</td><td>2982 (9.4)</td><td>52 (8.6)</td><td rowspan="2">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="2">0.074</td></tr><tr><td>1</td><td>13471 (41.5)</td><td>13248 (41.5)</td><td>223 (36.9)</td></tr><tr><td rowspan="2">Qualifications - visit 2, n (%)</td><td>No</td><td>26781 (82.4)</td><td>26287 (82.4)</td><td>494 (81.7)</td><td rowspan="2">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="2">0.294</td></tr><tr><td>Yes other</td><td>5717 (17.6)</td><td>5606 (17.6)</td><td>111 (18.3)</td></tr><tr><td rowspan="2">Scanner lateral (x) brain position - visit 2, mean (SD)</td><td>A levels/AS levels or equivalent</td><td>644 (2.0)</td><td>629 (2.0)</td><td>15 (2.5)</td><td rowspan="2">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="2">0.379</td></tr><tr><td>CSEs or equivalent</td><td>45 (0.1)</td><td>42 (0.1)</td><td>3 (0.5)</td></tr><tr><td>Scanner longitudinal (z) brain position - visit 2, mean (SD)</td><td>College or University degree</td><td>4013 (12.3)</td><td>3944 (12.4)</td><td>69 (11.4)</td><td>Two Sample T-test</td><td>-0.036</td></tr><tr><td>Scanner table position - visit 2, mean (SD)</td><td>NVQ or HND or HNC or equivalent</td><td>1205 (3.7)</td><td>1169 (3.7)</td><td>36 (6.0)</td><td>Two Sample T-test</td><td>0.095</td></tr><tr><td>Scanner transverse (y) brain position - visit 2, mean (SD)</td><td>None of the above</td><td>16203 (49.9)</td><td>15972 (50.1)</td><td>231 (38.2)</td><td>Two Sample T-test</td><td>-0.126</td></tr><tr><td>Self declared mental exclude visit 2, mean (SD)</td><td>O levels/GCSEs or equivalent</td><td>1901 (5.8)</td><td>1859 (5.8)</td><td>42 (6.9)</td><td>Two Sample T-test</td><td>-0.053</td></tr><tr><td rowspan="2">Sex - visit 0, n (%)</td><td>Other professional qualifications eg: nursing, teaching other</td><td>1762 (5.4)</td><td>1714 (5.4)</td><td>48 (7.9)</td><td>Two Sample T-test</td><td>0.035</td></tr><tr><td></td><td>1596 (4.9)</td><td>5571 (17.5)</td><td>146 (24.1)</td><td>Chi-squared</td><td>0.135</td></tr><tr><td rowspan="2">Social support, n (%)</td><td>Female</td><td>101 (0.3)</td><td>95 (0.3)</td><td>6 (1.0)</td><td>Chi-squared</td><td>0.076</td></tr><tr><td>Male</td><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.6 (3.0)</td><td>Chi-squared</td><td>0.068</td></tr><tr><td></td><td>False</td><td>17195 (52.9)</td><td>16915 (53.0)</td><td>280 (46.3)</td><td>Chi-squared</td><td>0.001</td></tr><tr><td></td><td></td><td>15303 (47.1)</td><td>14978 (47.0)</td><td>325 (53.7)</td><td>Chi-squared</td><td>0.003</td></tr><tr><td></td><td></td><td>12720 (39.1)</td><td>12461 (39.1)</td><td>259 (42.8)</td><td>Chi-squared</td><td>0.001</td></tr></tbody></table>
...continued

<table><caption>Table S13: Baseline characteristics of the included participants, according to their current smoker status versus never smokers. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure being a current smoker, and no treatment being a never smoker). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>No current smoking</th><th>Current smoking</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="4"></td><td rowspan="4">Total alcohol weekly units 2, mean (SD)<br/>Townsend deprivation index at recruitment - visit 0, mean (SD)<br/>Uk biobank assessment centre - visit 2, n (%)</td><td>True</td><td>19778 (60.9)<br/>13.1 (14.4)<br/>-1.9 (2.7)</td><td>19432 (60.9)<br/>13.0 (14.2)<br/>-1.9 (2.7)</td><td>346 (57.2)<br/>19.2 (22.4)<br/>-0.7 (3.2)</td><td>&lt;0.001<br/>&lt;0.001</td><td>Two Sample T-test<br/>Two Sample T-test</td><td>0.329<br/>0.434</td></tr><tr><td>Cheadle</td><td>18991 (58.4)</td><td>18598 (58.3)</td><td>393 (65.0)</td><td>0.003</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.152</td></tr><tr><td>Newcastle</td><td>8436 (26.0)</td><td>8311 (26.1)</td><td>125 (20.7)</td><td></td><td></td><td></td></tr><tr><td>Reading other</td><td>5028 (15.5)<br/>43 (0.1)<br/>1.3 (0.1)</td><td>4943 (15.5)<br/>41 (0.1)<br/>1.3 (0.1)</td><td>85 (14.0)<br/>2 (0.3)<br/>1.3 (0.1)</td><td>0.587</td><td>Two Sample T-test</td><td>-0.023</td></tr><tr><td></td><td>Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Never smoker</th><th>Current smoker</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10">Sample size<br/>Outcome<br/>Mediators</td><td>n</td><td></td><td>21203</td><td>20598</td><td>605</td><td></td><td></td><td></td></tr><tr><td>G factor, mean (SD)</td><td></td><td>-0.1 (1.1)</td><td>-0.1 (1.1)</td><td>0.1 (1.1)</td><td>0.001</td><td>Two Sample T-test</td><td>0.132</td></tr><tr><td>Dmri pc 0, mean (SD)</td><td></td><td>-0.8 (10.0)</td><td>-0.8 (10.0)</td><td>0.7 (10.6)</td><td>0.001</td><td>Two Sample T-test</td><td>0.147</td></tr><tr><td>Dmri pc 1, mean (SD)</td><td></td><td>0.4 (5.2)</td><td>0.4 (5.2)</td><td>0.3 (5.1)</td><td>0.698</td><td>Two Sample T-test</td><td>-0.016</td></tr><tr><td>Dmri pc 2, mean (SD)</td><td></td><td>-0.3 (5.0)</td><td>-0.3 (5.0)</td><td>-0.1 (4.5)</td><td>0.275</td><td>Two Sample T-test</td><td>0.043</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td></td><td>-0.1 (4.4)</td><td>-0.1 (4.4)</td><td>0.8 (4.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.228</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td></td><td>-0.0 (4.2)</td><td>-0.0 (4.2)</td><td>0.2 (4.2)</td><td>0.139</td><td>Two Sample T-test</td><td>0.061</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td></td><td>0.0 (3.4)</td><td>0.0 (3.4)</td><td>-0.2 (3.5)</td><td>0.101</td><td>Two Sample T-test</td><td>-0.068</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td></td><td>-0.9 (10.3)</td><td>-1.0 (10.3)</td><td>0.5 (10.9)</td><td>0.001</td><td>Two Sample T-test</td><td>0.137</td></tr><tr><td>Smri dmri pc 1, mean (SD)</td><td></td><td>-0.2 (7.5)</td><td>-0.2 (7.5)</td><td>-0.7 (7.5)</td><td>0.117</td><td>Two Sample T-test</td><td>-0.065</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td></td><td>0.5 (5.5)</td><td>0.5 (5.5)</td><td>0.5 (5.4)</td><td>0.873</td><td>Two Sample T-test</td><td>-0.007</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td></td><td>-0.0 (4.7)</td><td>-0.0 (4.7)</td><td>0.4 (4.2)</td><td>0.010</td><td>Two Sample T-test</td><td>0.100</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td></td><td>-0.2 (4.3)</td><td>-0.2 (4.3)</td><td>0.7 (3.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.222</td></tr><tr><td>Smri dmri pc 5, mean (SD)</td><td></td><td>0.1 (4.3)</td><td>0.1 (4.3)</td><td>0.3 (4.3)</td><td>0.171</td><td>Two Sample T-test</td><td>0.057</td></tr><tr><td>Smri pc 0, mean (SD)</td><td></td><td>0.5 (7.2)</td><td>0.5 (7.2)</td><td>0.5 (7.3)</td><td>0.875</td><td>Two Sample T-test</td><td>0.007</td></tr><tr><td>Smri pc 1, mean (SD)</td><td></td><td>-0.2 (3.3)</td><td>-0.2 (3.3)</td><td>0.3 (3.3)</td><td>0.002</td><td>Two Sample T-test</td><td>0.132</td></tr><tr><td>Smri pc 2, mean (SD)</td><td></td><td>-0.3 (2.7)</td><td>-0.3 (2.7)</td><td>-0.3 (2.9)</td><td>0.969</td><td>Two Sample T-test</td><td>0.002</td></tr><tr><td>Smri pc 3, mean (SD)</td><td></td><td>-0.0 (2.1)</td><td>-0.0 (2.0)</td><td>0.3 (2.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.151</td></tr><tr><td rowspan="15">Confounders (alphabetic order)</td><td>Adopted as a child - visit 0, n (%)</td><td>No</td><td>21185 (99.9)</td><td>20583 (99.9)</td><td>602 (99.5)</td><td>0.002</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.080</td></tr><tr><td rowspan="2">Yes<br/>other</td><td></td><td>6 (0.0)</td><td>5 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>12 (0.1)</td><td>10 (0.0)</td><td>2 (0.3)</td><td></td><td></td><td></td></tr><tr><td>Age when attended assessment centre - visit 2, mean (SD)</td><td></td><td>63.1 (7.6)</td><td>63.2 (7.6)</td><td>60.9 (7.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.302</td></tr><tr><td rowspan="2">Alcohol above nhs reco, n (%)</td><td>0</td><td>15119 (71.3)</td><td>14789 (71.8)</td><td>330 (54.5)</td><td></td><td></td><td></td></tr><tr><td>1</td><td>6084 (28.7)</td><td>5809 (28.2)</td><td>275 (45.5)</td><td></td><td></td><td></td></tr><tr><td rowspan="7">Alcohol intake frequency. - visit 2, n (%)</td><td>Daily or almost daily</td><td>2891 (13.6)</td><td>2731 (13.3)</td><td>160 (26.4)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.364</td></tr><tr><td>Never</td><td>1473 (6.9)</td><td>1429 (6.9)</td><td>44 (7.3)</td><td></td><td></td><td></td></tr><tr><td>Once or twice a week</td><td>6006 (28.3)</td><td>5865 (28.5)</td><td>141 (23.3)</td><td></td><td></td><td></td></tr><tr><td>One to three times a month</td><td>2742 (12.9)</td><td>2667 (12.9)</td><td>75 (12.4)</td><td></td><td></td><td></td></tr><tr><td>Special occasions only</td><td>2410 (11.4)</td><td>2332 (11.3)</td><td>78 (12.9)</td><td></td><td></td><td></td></tr><tr><td>Three or four times a week</td><td>5681 (26.8)</td><td>5574 (27.1)</td><td>107 (17.7)</td><td></td><td></td><td></td></tr><tr><td>18,000 to 30,999</td><td>4936 (23.3)</td><td>4777 (23.2)</td><td>159 (26.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.300</td></tr><tr><td rowspan="7">Average total household income before tax - visit 2, n (%)</td><td>31,000 to 51,999</td><td></td><td>5917 (27.9)</td><td>5771 (28.0)</td><td>146 (24.1)</td><td></td><td></td><td></td></tr><tr><td>52,000 to 100,000</td><td></td><td>4734 (22.3)</td><td>4629 (22.5)</td><td>105 (17.4)</td><td></td><td></td><td></td></tr><tr><td>Do not know</td><td></td><td>641 (3.0)</td><td>624 (3.0)</td><td>17 (2.8)</td><td></td><td></td><td></td></tr><tr><td>Greater than 100,000</td><td></td><td>1570 (7.4)</td><td>1542 (7.5)</td><td>28 (4.6)</td><td></td><td></td><td></td></tr><tr><td>Less than 18,000</td><td></td><td>2145 (10.1)</td><td>2034 (9.9)</td><td>111 (18.3)</td><td></td><td></td><td></td></tr><tr><td>Prefer not to answer</td><td></td><td>1260 (5.9)</td><td>1221 (5.9)</td><td>39 (6.4)</td><td></td><td></td><td></td></tr><tr><td>Body mass index (bmi) - visit 2, mean (SD)</td><td></td><td>26.2 (4.3)</td><td>26.2 (4.3)</td><td>26.5 (4.7)</td><td>0.100</td><td>Two Sample T-test</td><td>0.070</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Never smoker</th><th>Current smoker</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td></td><td>Breastfed as a baby - visit 0, n (%)</td><td>Do not know</td><td>3867 (18.2)</td><td>3743 (18.2)</td><td>124 (20.5)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.123</td></tr><tr><td></td><td>Cmdd final, n (%)</td><td>No</td><td>4922 (23.2)</td><td>4767 (23.1)</td><td>155 (25.6)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Yes</td><td>12406 (58.5)</td><td>12082 (58.7)</td><td>324 (53.6)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.3)</td><td></td><td></td><td></td></tr><tr><td></td><td>Comparative body size at age 10 - visit 0, n (%)</td><td>False</td><td>15583 (73.5)</td><td>15206 (73.8)</td><td>377 (62.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.249</td></tr><tr><td></td><td></td><td>True</td><td>5620 (26.5)</td><td>5392 (26.2)</td><td>228 (37.7)</td><td>0.012</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.108</td></tr><tr><td></td><td>Comparative height size at age 10 - visit 0, n (%)</td><td>About average</td><td>10933 (51.6)</td><td>10630 (51.6)</td><td>303 (50.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Do not know</td><td>251 (1.2)</td><td>243 (1.2)</td><td>8 (1.3)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Plumper</td><td>3154 (14.9)</td><td>3044 (14.8)</td><td>110 (18.2)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Thinner</td><td>6861 (32.4)</td><td>6678 (32.4)</td><td>183 (30.2)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>4 (0.0)</td><td>3 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Comparative height size at age 10 - visit 0, n (%)</td><td>About average</td><td>11087 (52.3)</td><td>10787 (52.4)</td><td>300 (49.6)</td><td>0.037</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.086</td></tr><tr><td></td><td></td><td>Do not know</td><td>216 (1.0)</td><td>207 (1.0)</td><td>9 (1.5)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Shorter</td><td>4333 (20.4)</td><td>4199 (20.4)</td><td>134 (22.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Taller</td><td>5563 (26.2)</td><td>5402 (26.2)</td><td>161 (26.6)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>4 (0.0)</td><td>3 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>Elsewhere</td><td>1180 (5.6)</td><td>1151 (5.6)</td><td>29 (4.8)</td><td>0.313</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.084</td></tr><tr><td></td><td></td><td>England</td><td>17850 (84.2)</td><td>17342 (84.2)</td><td>508 (84.0)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Northern Ireland</td><td>132 (0.6)</td><td>125 (0.6)</td><td>7 (1.2)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Republic of Ireland</td><td>127 (0.6)</td><td>124 (0.6)</td><td>3 (0.5)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Scotland</td><td>1524 (7.2)</td><td>1478 (7.2)</td><td>46 (7.6)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Wales</td><td>383 (1.8)</td><td>372 (1.8)</td><td>11 (1.8)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>7 (0.0)</td><td>6 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Current employment status - visit 2, n (%)</td><td>In paid employment or self-employed</td><td>8827 (41.6)</td><td>8504 (41.3)</td><td>323 (53.4)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.327</td></tr><tr><td></td><td></td><td>Retired</td><td>11549 (54.5)</td><td>11311 (54.9)</td><td>238 (39.3)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>827 (3.9)</td><td>783 (3.8)</td><td>44 (7.3)</td><td></td><td></td><td></td></tr><tr><td></td><td>Diabetic, n (%)</td><td>0</td><td>20446 (96.4)</td><td>19881 (96.5)</td><td>565 (93.4)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.143</td></tr><tr><td></td><td></td><td>1</td><td>757 (3.6)</td><td>717 (3.5)</td><td>40 (6.6)</td><td></td><td></td><td></td></tr><tr><td></td><td>Ethnic background - visit 2, n (%)</td><td>British</td><td>4749 (22.4)</td><td>4581 (22.2)</td><td>168 (27.8)</td><td>0.002</td><td>Chi-squared</td><td>0.128</td></tr><tr><td></td><td></td><td>other</td><td>16454 (77.6)</td><td>16017 (77.8)</td><td>437 (72.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Handedness (chirality/laterality) - visit 0, n (%)</td><td>Left-handed</td><td>1937 (9.1)</td><td>1878 (9.1)</td><td>59 (9.8)</td><td>0.165</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.068</td></tr><tr><td></td><td></td><td>Right-handed</td><td>18929 (89.3)</td><td>18397 (89.3)</td><td>532 (87.9)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Use both right and left hands equally</td><td>330 (1.6)</td><td>317 (1.5)</td><td>13 (2.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>7 (0.0)</td><td>6 (0.0)</td><td>1 (0.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Hypercholesterol, n (%)</td><td>0</td><td>16554 (78.1)</td><td>16105 (78.2)</td><td>449 (74.2)</td><td>0.023</td><td>Chi-squared</td><td>0.093</td></tr><tr><td></td><td></td><td>1</td><td>4649 (21.9)</td><td>4493 (21.8)</td><td>156 (25.8)</td><td></td><td></td><td></td></tr><tr><td></td><td>Hypertensive, n (%)</td><td>0</td><td>16050 (75.7)</td><td>15585 (75.7)</td><td>465 (76.9)</td><td>0.530</td><td>Chi-squared</td><td>0.028</td></tr><tr><td></td><td></td><td>1</td><td>5153 (24.3)</td><td>5013 (24.3)</td><td>140 (23.1)</td><td></td><td></td><td></td></tr><tr><td></td><td>Inflammation, n (%)</td><td>False</td><td>17986 (84.8)</td><td>17539 (85.1)</td><td>447 (73.9)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.282</td></tr><tr><td></td><td></td><td>True</td><td>3217 (15.2)</td><td>3059 (14.9)</td><td>158 (26.1)</td><td></td><td></td><td></td></tr><tr><td></td><td>Job involves shift work - visit 2, n (%)</td><td>Always</td><td>531 (2.5)</td><td>498 (2.4)</td><td>33 (5.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.270</td></tr><tr><td></td><td></td><td>Never/rarely</td><td>7569 (35.7)</td><td>7321 (35.5)</td><td>248 (41.0)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Sometimes</td><td>549 (2.6)</td><td>518 (2.5)</td><td>31 (5.1)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>12554 (59.2)</td><td>12261 (59.5)</td><td>293 (48.4)</td><td></td><td></td><td></td></tr><tr><td></td><td>Length of time at current address - visit 2, mean (SD)</td><td></td><td>21.2 (13.8)</td><td>21.3 (13.8)</td><td>17.7 (13.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.271</td></tr><tr><td></td><td>Life long depression, n (%)</td><td>False</td><td>18098 (85.4)</td><td>17619 (85.5)</td><td>479 (79.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.168</td></tr><tr><td></td><td></td><td>True</td><td>3105 (14.6)</td><td>2979 (14.5)</td><td>126 (20.8)</td><td></td><td></td><td></td></tr><tr><td></td><td>Ls pc dim.1, mean (SD)</td><td></td><td>0.6 (2.0)</td><td>0.6 (2.0)</td><td>0.2 (2.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.167</td></tr><tr><td></td><td>Ls pc dim.2, mean (SD)</td><td></td><td>-0.3 (2.0)</td><td>-0.3 (2.0)</td><td>-1.2 (2.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.412</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Never smoker</th><th>Current smoker</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td></td><td>Maternal smoking around birth - visit 0, n (%)</td><td>Do not know</td><td>2029 (9.6)</td><td>1934 (9.4)</td><td>95 (15.7)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.276</td></tr><tr><td></td><td>Mh pc dim.1, mean (SD)</td><td>No</td><td>13528 (63.8)</td><td>13215 (64.2)</td><td>313 (51.7)</td><td></td><td></td><td></td></tr><tr><td></td><td>Mh pc dim.2, mean (SD)</td><td>Yes</td><td>5636 (26.6)</td><td>5441 (26.4)</td><td>195 (32.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Number in household - visit 2, mean (SD)</td><td>other</td><td>10 (0.0)</td><td>8 (0.0)</td><td>2 (0.3)</td><td></td><td></td><td></td></tr><tr><td></td><td>Number of full brothers - visit 2, mean (SD)</td><td></td><td>1.3 (6.4)</td><td>1.4 (6.3)</td><td>-1.8 (7.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.476</td></tr><tr><td></td><td>Number of full sisters - visit 2, mean (SD)</td><td></td><td>0.5 (3.3)</td><td>0.5 (3.2)</td><td>-0.2 (3.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.191</td></tr><tr><td></td><td>Number of vehicles in household - visit 2, n (%)</td><td>Four or more</td><td>2.2 (1.0)</td><td>2.2 (1.0)</td><td>2.0 (1.2)</td><td>0.007</td><td>Two Sample T-test</td><td>-0.119</td></tr><tr><td></td><td>Obesity, n (%)</td><td></td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.2 (1.3)</td><td>0.001</td><td>Two Sample T-test</td><td>0.153</td></tr><tr><td></td><td>Part of a multiple birth - visit 0, n (%)</td><td></td><td>0.9 (1.1)</td><td>0.9 (1.1)</td><td>1.2 (1.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.219</td></tr><tr><td></td><td></td><td>None</td><td>798 (3.8)</td><td>750 (3.6)</td><td>48 (7.9)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>One</td><td>8706 (41.1)</td><td>8438 (41.0)</td><td>268 (44.3)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Three</td><td>2098 (9.9)</td><td>2046 (9.9)</td><td>52 (8.6)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Two</td><td>8926 (42.1)</td><td>8703 (42.3)</td><td>223 (36.9)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>25 (0.1)</td><td>23 (0.1)</td><td>2 (0.3)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>0</td><td>17739 (83.7)</td><td>17245 (83.7)</td><td>494 (81.7)</td><td>0.193</td><td>Chi-squared</td><td>0.055</td></tr><tr><td></td><td></td><td>1</td><td>3464 (16.3)</td><td>3353 (16.3)</td><td>111 (18.3)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>No</td><td>20720 (97.7)</td><td>20133 (97.7)</td><td>587 (97.0)</td><td>0.044</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.071</td></tr><tr><td></td><td>Qualifications - visit 2, n (%)</td><td></td><td>Yes</td><td>454 (2.1)</td><td>439 (2.1)</td><td>15 (2.5)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>29 (0.1)</td><td>26 (0.1)</td><td>3 (0.5)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>A levels/AS levels or equivalent</td><td>2637 (12.4)</td><td>2568 (12.5)</td><td>69 (11.4)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.348</td></tr><tr><td></td><td>Scanner lateral (x) brain position - visit 2, mean (SD)</td><td>CSEs or equivalent</td><td>767 (3.6)</td><td>731 (3.5)</td><td>36 (6.0)</td><td></td><td></td><td></td></tr><tr><td></td><td>Scanner longitudinal (z) brain position - visit 2, mean (SD)</td><td>College or University degree</td><td>11038 (52.1)</td><td>10807 (52.5)</td><td>231 (38.2)</td><td></td><td></td><td></td></tr><tr><td></td><td>Scanner table position - visit 2, mean (SD)</td><td>NVQ or HND or HNC or equivalent</td><td>1094 (5.2)</td><td>1052 (5.1)</td><td>42 (6.9)</td><td></td><td></td><td></td></tr><tr><td></td><td>Scanner transverse (y) brain position - visit 2, mean (SD)</td><td>None of the above</td><td>972 (4.6)</td><td>924 (4.5)</td><td>48 (7.9)</td><td></td><td></td><td></td></tr><tr><td></td><td>Self declared mental exclusion visit 2, mean (SD)</td><td>O levels/GCSEs or equivalent</td><td>3603 (17.0)</td><td>3457 (16.8)</td><td>146 (24.1)</td><td></td><td></td><td></td></tr><tr><td></td><td>Sex - visit 0, n (%)</td><td>Other professional qualifications eg: nursing, teaching other</td><td>1028 (4.8)</td><td>1001 (4.9)</td><td>27 (4.5)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>64 (0.3)</td><td>58 (0.3)</td><td>6 (1.0)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>0.7 (3.0)</td><td>0.7 (3.0)</td><td>0.6 (3.0)</td><td>0.472</td><td>Two Sample T-test</td><td>-0.029</td></tr><tr><td></td><td></td><td>Female</td><td>-27.7 (26.6)</td><td>-27.8 (26.5)</td><td>-25.5 (28.7)</td><td>0.053</td><td>Two Sample T-test</td><td>0.083</td></tr><tr><td></td><td></td><td>Male</td><td>-1054.1 (24.9)</td><td>-1054.0 (24.8)</td><td>-1057.5 (27.4)</td><td>0.002</td><td>Two Sample T-test</td><td>-0.133</td></tr><tr><td></td><td></td><td>False</td><td>66.3 (6.0)</td><td>66.3 (6.0)</td><td>66.1 (5.7)</td><td>0.298</td><td>Two Sample T-test</td><td>-0.042</td></tr><tr><td></td><td></td><td>True</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.360</td><td>Two Sample T-test</td><td>0.040</td></tr><tr><td></td><td>Total alcohol weekly units 2, mean (SD)</td><td></td><td>11717 (55.3)</td><td>11437 (55.5)</td><td>280 (46.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.186</td></tr><tr><td></td><td>Townsend deprivation index at recruitment - visit 0, mean (SD)</td><td></td><td>9486 (44.7)</td><td>9161 (44.5)</td><td>325 (53.7)</td><td></td><td></td><td></td></tr><tr><td></td><td>Uk biobank assessment centre - visit 2, n (%)</td><td></td><td>8135 (38.4)</td><td>7876 (38.2)</td><td>259 (42.8)</td><td>0.025</td><td>Chi-squared</td><td>0.093</td></tr><tr><td></td><td></td><td>Female</td><td>13068 (61.6)</td><td>12722 (61.8)</td><td>346 (57.2)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>True</td><td>11.2 (13.0)</td><td>11.0 (12.6)</td><td>19.2 (22.4)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.449</td></tr><tr><td></td><td></td><td></td><td>-2.1 (2.6)</td><td>-2.1 (2.6)</td><td>-0.7 (3.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.491</td></tr><tr><td></td><td></td><td>Cheadle</td><td>12339 (58.2)</td><td>11946 (58.0)</td><td>393 (65.0)</td><td>0.002</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.161</td></tr><tr><td></td><td></td><td>Newcastle</td><td>5625 (26.5)</td><td>5500 (26.7)</td><td>125 (20.7)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>Reading</td><td>3209 (15.1)</td><td>3124 (15.2)</td><td>85 (14.0)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td>other</td><td>30 (0.1)</td><td>28 (0.1)</td><td>2 (0.3)</td><td></td><td></td><td></td></tr></tbody></table>
...continued

<table><caption>Table S14: Baseline characteristics of the included participants, according to their previous smoker status versus never smokers. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure being a previous smoker, and no treatment being a never smoker). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Never smoker</th><th>Current smoker</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td></td><td>Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td></td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>1.3 (0.1)</td><td>0.187</td><td>Two Sample T-test</td><td>-0.056</td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Never smoker</th><th>Previous smoker</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td>Sample size</td><td>n</td><td></td><td>31893</td><td>20598</td><td>11295</td><td></td><td></td><td></td></tr><tr><td>Outcome</td><td>G factor, mean (SD)</td><td></td><td>-0.0 (1.1)</td><td>-0.1 (1.1)</td><td>-0.0 (1.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.051</td></tr><tr><td rowspan="10">Mediators</td><td>Dmri pc 0, mean (SD)</td><td></td><td>-0.3 (10.2)</td><td>-0.8 (10.0)</td><td>0.7 (10.6)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.148</td></tr><tr><td>Dmri pc 1, mean (SD)</td><td></td><td>0.1 (5.2)</td><td>0.4 (5.2)</td><td>-0.5 (5.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.167</td></tr><tr><td>Dmri pc 2, mean (SD)</td><td></td><td>-0.1 (5.0)</td><td>-0.3 (5.0)</td><td>0.2 (5.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.100</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td></td><td>-0.0 (4.4)</td><td>-0.1 (4.4)</td><td>0.2 (4.4)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.087</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td></td><td>0.0 (4.2)</td><td>-0.0 (4.2)</td><td>0.1 (4.3)</td><td>0.085</td><td>Two Sample T-test</td><td>0.020</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td></td><td>0.0 (3.4)</td><td>0.0 (3.4)</td><td>-0.0 (3.5)</td><td>0.025</td><td>Two Sample T-test</td><td>-0.026</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td></td><td>-0.4 (10.5)</td><td>-1.0 (10.3)</td><td>0.7 (10.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.164</td></tr><tr><td>Smri dmri pc 1, mean (SD)</td><td></td><td>-0.2 (7.4)</td><td>-0.2 (7.5)</td><td>-0.1 (7.3)</td><td>0.298</td><td>Two Sample T-test</td><td>0.012</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td></td><td>0.1 (5.6)</td><td>0.5 (5.5)</td><td>-0.6 (5.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.186</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td></td><td>-0.0 (4.7)</td><td>-0.0 (4.7)</td><td>0.0 (4.7)</td><td>0.465</td><td>Two Sample T-test</td><td>0.009</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td></td><td>-0.0 (4.3)</td><td>-0.2 (4.3)</td><td>0.3 (4.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.122</td></tr><tr><td>Smri dmri pc 5, mean (SD)</td><td></td><td>0.0 (4.3)</td><td>0.1 (4.3)</td><td>0.0 (4.3)</td><td>0.414</td><td>Two Sample T-test</td><td>-0.010</td></tr><tr><td>Smri pc 0, mean (SD)</td><td></td><td>0.3 (7.2)</td><td>0.5 (7.2)</td><td>-0.2 (7.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.094</td></tr><tr><td>Smri pc 1, mean (SD)</td><td></td><td>-0.0 (3.3)</td><td>-0.2 (3.3)</td><td>0.2 (3.4)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.110</td></tr><tr><td>Smri pc 2, mean (SD)</td><td></td><td>-0.1 (2.8)</td><td>-0.3 (2.7)</td><td>0.3 (2.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.204</td></tr><tr><td>Smri pc 3, mean (SD)</td><td></td><td>-0.0 (2.1)</td><td>-0.0 (2.0)</td><td>0.1 (2.1)</td><td>0.001</td><td>Two Sample T-test</td><td>0.039</td></tr><tr><td rowspan="10">Confounders (alphabetic order)</td><td>Adopted as a child - visit 0, n (%)</td><td>No</td><td>31867 (99.9)</td><td>20583 (99.9)</td><td>11284 (99.9)</td><td>0.720</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.009</td></tr><tr><td rowspan="2">Age when attended assessment centre - visit 2, mean (SD)</td><td>Yes</td><td>8 (0.0)</td><td>5 (0.0)</td><td>3 (0.0)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>18 (0.1)</td><td>10 (0.0)</td><td>8 (0.1)</td><td></td><td></td><td></td></tr><tr><td>Alcohol above nhs reco, n (%)</td><td>0</td><td>20926 (65.6)</td><td>14789 (71.8)</td><td>6137 (54.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.213</td></tr><tr><td rowspan="7">Alcohol intake frequency. - visit 2, n (%)</td><td>1</td><td>10967 (34.4)</td><td>5809 (28.2)</td><td>5158 (45.7)</td><td></td><td></td><td></td></tr><tr><td>Daily or almost daily</td><td>5380 (16.9)</td><td>2731 (13.3)</td><td>2649 (23.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.368</td></tr><tr><td>Never</td><td>1988 (6.2)</td><td>1429 (6.9)</td><td>559 (4.9)</td><td></td><td></td><td></td></tr><tr><td>Once or twice a week</td><td>8499 (26.6)</td><td>5865 (28.5)</td><td>2634 (23.3)</td><td></td><td></td><td></td></tr><tr><td>One to three times a month</td><td>3713 (11.6)</td><td>2667 (12.9)</td><td>1046 (9.3)</td><td></td><td></td><td></td></tr><tr><td>Special occasions only</td><td>3184 (10.0)</td><td>2332 (11.3)</td><td>852 (7.5)</td><td></td><td></td><td></td></tr><tr><td>Three or four times a week</td><td>9129 (28.6)</td><td>5574 (27.1)</td><td>3555 (31.5)</td><td></td><td></td><td></td></tr><tr><td>Average total household income before tax - visit 2, n (%)</td><td>18,000 to 30,999</td><td>7654 (24.0)</td><td>4777 (23.2)</td><td>2877 (25.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.095</td></tr><tr><td rowspan="7">Body mass index (bmi) - visit 2, mean (SD)</td><td>31,000 to 51,999</td><td>9010 (28.3)</td><td>5771 (28.0)</td><td>3239 (28.7)</td><td></td><td></td><td></td></tr><tr><td>52,000 to 100,000</td><td>6923 (21.7)</td><td>4629 (22.5)</td><td>2294 (20.3)</td><td></td><td></td><td></td></tr><tr><td>Do not know</td><td>944 (3.0)</td><td>624 (3.0)</td><td>320 (2.8)</td><td></td><td></td><td></td></tr><tr><td>Greater than 100,000</td><td>2249 (7.1)</td><td>1542 (7.5)</td><td>707 (6.3)</td><td></td><td></td><td></td></tr><tr><td>Less than 18,000</td><td>3291 (10.3)</td><td>2034 (9.9)</td><td>1257 (11.1)</td><td></td><td></td><td></td></tr><tr><td>Prefer not to answer</td><td>1822 (5.7)</td><td>1221 (5.9)</td><td>601 (5.3)</td><td></td><td></td><td></td></tr><tr><td>Body mass index (bmi) - visit 2, mean (SD)</td><td>26.4 (4.3)</td><td>26.2 (4.3)</td><td>26.8 (4.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.154</td></tr><tr><td rowspan="4">Breastfed as a baby - visit 0, n (%)</td><td>Do not know</td><td>6051 (19.0)</td><td>3743 (18.2)</td><td>2308 (20.4)</td><td>&lt;0.001</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.087</td></tr><tr><td>No</td><td>7019 (22.0)</td><td>4767 (23.1)</td><td>2252 (19.9)</td><td></td><td></td><td></td></tr><tr><td>Yes</td><td>18812 (59.0)</td><td>12082 (58.7)</td><td>6730 (59.6)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>11 (0.0)</td><td>6 (0.0)</td><td>5 (0.0)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Cmdd final, n (%)</td><td>False</td><td>23036 (72.2)</td><td>15206 (73.8)</td><td>7830 (69.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.100</td></tr><tr><td>True</td><td>8857 (27.8)</td><td>5392 (26.2)</td><td>3465 (30.7)</td><td></td><td></td><td></td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Never smoker</th><th>Previous smoker</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="10"></td><td rowspan="3">Comparative body size at age 10 - visit 0, n (%)</td><td>About average</td><td>16334 (51.2)</td><td>10630 (51.6)</td><td>5704 (50.5)</td><td>0.005</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.046</td></tr><tr><td>Do not know</td><td>339 (1.1)</td><td>243 (1.2)</td><td>96 (0.8)</td><td></td><td></td><td></td></tr><tr><td>Plumper</td><td>4812 (15.1)</td><td>3044 (14.8)</td><td>1768 (15.7)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Comparative height size at age 10 - visit 0, n (%)</td><td>Thinner</td><td>10401 (32.6)</td><td>6678 (32.4)</td><td>3723 (33.0)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>7 (0.0)</td><td>3 (0.0)</td><td>4 (0.0)</td><td></td><td></td><td></td></tr><tr><td>About average</td><td>16739 (52.5)</td><td>10787 (52.4)</td><td>5952 (52.7)</td><td>0.015</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.042</td></tr><tr><td rowspan="3">Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>Do not know</td><td>284 (0.9)</td><td>207 (1.0)</td><td>77 (0.7)</td><td></td><td></td><td></td></tr><tr><td>Shorter</td><td>6435 (20.2)</td><td>4199 (20.4)</td><td>2236 (19.8)</td><td></td><td></td><td></td></tr><tr><td>Taller</td><td>8428 (26.4)</td><td>5402 (26.2)</td><td>3026 (26.8)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Current employment status - visit 2, n (%)</td><td>other</td><td>7 (0.0)</td><td>3 (0.0)</td><td>4 (0.0)</td><td></td><td></td><td></td></tr><tr><td>Elsewhere</td><td>1749 (5.5)</td><td>1151 (5.6)</td><td>598 (5.3)</td><td>0.009</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.047</td></tr><tr><td>England</td><td>26852 (84.2)</td><td>17342 (84.2)</td><td>9510 (84.2)</td><td></td><td></td><td></td></tr><tr><td rowspan="5">Diabetic, n (%)</td><td>Northern Ireland</td><td>227 (0.7)</td><td>125 (0.6)</td><td>102 (0.9)</td><td></td><td></td><td></td></tr><tr><td>Republic of Ireland</td><td>214 (0.7)</td><td>124 (0.6)</td><td>90 (0.8)</td><td></td><td></td><td></td></tr><tr><td>Scotland</td><td>2250 (7.1)</td><td>1478 (7.2)</td><td>772 (6.8)</td><td></td><td></td><td></td></tr><tr><td>Wales</td><td>589 (1.8)</td><td>372 (1.8)</td><td>217 (1.9)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>12 (0.0)</td><td>6 (0.0)</td><td>6 (0.1)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Ethnic background - visit 2, n (%)</td><td>In paid employment or self-employed</td><td>12655 (39.7)</td><td>8504 (41.3)</td><td>4151 (36.8)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.099</td></tr><tr><td>Retired</td><td>18064 (56.6)</td><td>11311 (54.9)</td><td>6753 (59.8)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>1174 (3.7)</td><td>783 (3.8)</td><td>391 (3.5)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Handedness (chirality/laterality) - visit 0, n (%)</td><td>0</td><td>30589 (95.9)</td><td>19881 (96.5)</td><td>10708 (94.8)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.084</td></tr><tr><td>1</td><td>1304 (4.1)</td><td>717 (3.5)</td><td>587 (5.2)</td><td></td><td></td><td></td></tr><tr><td>British</td><td>7240 (22.7)</td><td>4581 (22.2)</td><td>2659 (23.5)</td><td>0.008</td><td>Chi-squared</td><td>0.031</td></tr><tr><td rowspan="3">Right-handed</td><td>other</td><td>24653 (77.3)</td><td>16017 (77.8)</td><td>8636 (76.5)</td><td></td><td></td><td></td></tr><tr><td>Left-handed</td><td>2984 (9.4)</td><td>1878 (9.1)</td><td>1106 (9.8)</td><td>0.139</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.027</td></tr><tr><td>Use both right and left hands equally</td><td>28425 (89.1)</td><td>18397 (89.3)</td><td>10028 (88.8)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Hypercholesterol, n (%)</td><td>other</td><td>11 (0.0)</td><td>317 (1.5)</td><td>156 (1.4)</td><td></td><td></td><td></td></tr><tr><td>0</td><td>24089 (75.5)</td><td>16105 (78.2)</td><td>7984 (70.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.173</td></tr><tr><td>1</td><td>7804 (24.5)</td><td>4493 (21.8)</td><td>3311 (29.3)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Hypertensive, n (%)</td><td>0</td><td>23497 (73.7)</td><td>15585 (75.7)</td><td>7912 (70.0)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.126</td></tr><tr><td>1</td><td>8396 (26.3)</td><td>5013 (24.3)</td><td>3383 (30.0)</td><td></td><td></td><td></td></tr><tr><td>False</td><td>26820 (84.1)</td><td>17539 (85.1)</td><td>9281 (82.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.081</td></tr><tr><td rowspan="3">Inflammation, n (%)</td><td>True</td><td>5073 (15.9)</td><td>3059 (14.9)</td><td>2014 (17.8)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.097</td></tr><tr><td>Always</td><td>762 (2.4)</td><td>498 (2.4)</td><td>264 (2.3)</td><td></td><td></td><td></td></tr><tr><td>Never/rarely</td><td>10829 (34.0)</td><td>7321 (35.5)</td><td>3508 (31.1)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Job involves shift work - visit 2, n (%)</td><td>Sometimes</td><td>824 (2.6)</td><td>518 (2.5)</td><td>306 (2.7)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>19478 (61.1)</td><td>12261 (59.5)</td><td>7217 (63.9)</td><td></td><td></td><td></td></tr><tr><td>Length of time at current address - visit 2, mean (SD)</td><td>21.1 (13.9)</td><td>21.3 (13.8)</td><td>20.6 (14.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.054</td></tr><tr><td rowspan="3">Life long depression, n (%)</td><td>False</td><td>26982 (84.6)</td><td>17619 (85.5)</td><td>9363 (82.9)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.073</td></tr><tr><td>True</td><td>4911 (15.4)</td><td>2979 (14.5)</td><td>1932 (17.1)</td><td></td><td></td><td></td></tr><tr><td>Ls pc dim.1, mean (SD)</td><td>0.6 (2.0)</td><td>0.6 (2.0)</td><td>0.7 (2.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.051</td></tr><tr><td rowspan="3">Maternal smoking around birth - visit 0, n (%)</td><td>Ls pc dim.2, mean (SD)</td><td>-0.4 (2.0)</td><td>-0.3 (2.0)</td><td>-0.7 (2.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.192</td></tr><tr><td>Do not know</td><td>3293 (10.3)</td><td>1934 (9.4)</td><td>1359 (12.0)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.097</td></tr><tr><td>No</td><td>20031 (62.8)</td><td>13215 (64.2)</td><td>6816 (60.3)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Mh pc dim.1, mean (SD)</td><td>Yes</td><td>8554 (26.8)</td><td>5441 (26.4)</td><td>3113 (27.6)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>15 (0.0)</td><td>8 (0.0)</td><td>7 (0.1)</td><td></td><td></td><td></td></tr><tr><td>Mh pc dim.2, mean (SD)</td><td>1.1 (6.5)</td><td>1.4 (6.3)</td><td>0.4 (6.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.152</td></tr><tr><td rowspan="3">Number in household - visit 2, mean (SD)</td><td>0.5 (3.3)</td><td>0.5 (3.2)</td><td>0.4 (3.4)</td><td>0.002</td><td>Two Sample T-test</td><td>-0.036</td></tr><tr><td>2.2 (1.0)</td><td>2.2 (1.0)</td><td>2.1 (1.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.071</td></tr><tr><td>Number of full brothers - visit 2, mean (SD)</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.1 (1.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.057</td></tr></tbody></table>
...continued

<table><caption>Table S15: Baseline characteristics for the included participants, according to their weekly alcohol consumption, higher or lower than 14 units, the NHS recommendation. Adequate statistical tests depending on the variable type assess whether each variable has a distinct distributions between the "exposed" and the "unexposed" group (with exposure being consuming more than 14 weekly units of alcohol, and no treatment being consuming less than 14 weekly units of alcohol). We also report the Standardized mean difference (SMD) for each variable.</caption><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Never smoker</th><th>Previous smoker</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="2">Number of full sisters - visit 2, mean (SD)</td><td>Number of vehicles in household - visit 2, n (%)</td><td>Four or more</td><td>1.0 (1.1)<br>910 (2.9)</td><td>0.9 (1.1)<br>638 (3.1)</td><td>1.0 (1.1)<br>272 (2.4)</td><td>&lt;0.001<br>&lt;0.001</td><td>Two Sample T-test<br>Chi-squared</td><td>0.076<br>0.099</td></tr><tr><td>Obesity, n (%)</td><td>None<br>One<br>Three<br>Two<br>other</td><td>1217 (3.8)<br>13502 (42.3)<br>2982 (9.4)<br>13248 (41.5)<br>34 (0.1)</td><td>750 (3.6)<br>8438 (41.0)<br>2046 (9.9)<br>8703 (42.3)<br>23 (0.1)</td><td>467 (4.1)<br>5064 (44.8)<br>936 (8.3)<br>4545 (40.2)<br>11 (0.1)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Part of a multiple birth - visit 0, n (%)</td><td>0</td><td>0</td><td>26287 (82.4)<br>5606 (17.6)</td><td>17245 (83.7)<br>3353 (16.3)</td><td>9042 (80.1)<br>2253 (19.9)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.095</td></tr><tr><td>1</td><td>No</td><td>31222 (97.9)<br>629 (2.0)<br>42 (0.1)</td><td>20133 (97.7)<br>439 (2.1)<br>26 (0.1)</td><td>11089 (98.2)<br>190 (1.7)<br>16 (0.1)</td><td>0.021</td><td>Chi-squared</td><td>0.033</td></tr><tr><td rowspan="2">Qualifications - visit 2, n (%)</td><td>A levels/AS levels or equivalent</td><td>3944 (12.4)</td><td>2568 (12.5)</td><td>1376 (12.2)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.173</td></tr><tr><td>CSEs or equivalent</td><td>1169 (3.7)</td><td>731 (3.5)</td><td>438 (3.9)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Scanner lateral (x) brain position - visit 2, mean (SD)</td><td>College or University degree</td><td>15972 (50.1)</td><td>10807 (52.5)</td><td>5165 (45.7)</td><td></td><td></td><td></td></tr><tr><td>NVQ or HND or HNC or equivalent</td><td>1859 (5.8)</td><td>1052 (5.1)</td><td>807 (7.1)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Scanner longitudinal (z) brain position - visit 2, mean (SD)</td><td>None of the above</td><td>1714 (5.4)</td><td>924 (4.5)</td><td>790 (7.0)</td><td></td><td></td><td></td></tr><tr><td>O levels/GCSEs or equivalent</td><td>5571 (17.5)</td><td>3457 (16.8)</td><td>2114 (18.7)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Scanner table position - visit 2, mean (SD)</td><td>Other professional qualifications eg: nursing, teaching other</td><td>1569 (4.9)</td><td>1001 (4.9)</td><td>568 (5.0)</td><td></td><td></td><td></td></tr><tr><td></td><td>95 (0.3)<br>0.7 (3.0)</td><td>58 (0.3)<br>0.7 (3.0)</td><td>37 (0.3)<br>0.8 (3.0)</td><td>0.121</td><td>Two Sample T-test</td><td>0.018</td></tr><tr><td rowspan="2">Scanner transverse (y) brain position - visit 2, mean (SD)</td><td></td><td>-28.1 (26.7)</td><td>-27.8 (26.5)</td><td>-28.8 (27.0)</td><td>0.002</td><td>Two Sample T-test</td><td>-0.037</td></tr><tr><td></td><td>-1054.2 (25.0)</td><td>-1054.0 (24.8)</td><td>-1054.5 (25.4)</td><td>0.086</td><td>Two Sample T-test</td><td>-0.020</td></tr><tr><td rowspan="2">Self declared mental exclude visit 2, mean (SD)</td><td></td><td>66.4 (5.9)</td><td>66.3 (6.0)</td><td>66.5 (5.9)</td><td>0.010</td><td>Two Sample T-test</td><td>0.030</td></tr><tr><td></td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.0 (0.2)</td><td>0.293</td><td>Two Sample T-test</td><td>0.012</td></tr><tr><td rowspan="2">Sex - visit 0, n (%)</td><td>Female</td><td>16915 (53.0)</td><td>11437 (55.5)</td><td>5478 (48.5)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.141</td></tr><tr><td>Male</td><td>14978 (47.0)</td><td>9161 (44.5)</td><td>5817 (51.5)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Social support, n (%)</td><td>False</td><td>12461 (39.1)</td><td>7876 (38.2)</td><td>4585 (40.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.048</td></tr><tr><td>True</td><td>19432 (60.9)<br>13.0 (14.2)<br>-1.9 (2.7)</td><td>12722 (61.8)<br>11.0 (12.6)<br>-2.1 (2.6)</td><td>6710 (59.4)<br>16.6 (16.2)<br>-1.7 (2.8)</td><td>&lt;0.001<br>&lt;0.001</td><td>Two Sample T-test<br>Two Sample T-test</td><td>0.387<br>0.155</td></tr><tr><td rowspan="2">Total alcohol weekly units 2, mean (SD)</td><td>Uk biobank assessment centre - visit 2, n (%)</td><td>Cheadle</td><td>18598 (58.3)</td><td>11946 (58.0)</td><td>6652 (58.9)</td><td>0.002</td><td>Chi-squared</td><td>0.045</td></tr><tr><td></td><td>Newcastle</td><td>8311 (26.1)</td><td>5500 (26.7)</td><td>2811 (24.9)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Townsend deprivation index at recruitment - visit 0, mean (SD)</td><td></td><td>Reading</td><td>4943 (15.5)</td><td>3124 (15.2)</td><td>1819 (16.1)</td><td></td><td></td><td></td></tr><tr><td></td><td>other</td><td>41 (0.1)<br>1.3 (0.1)</td><td>28 (0.1)<br>1.3 (0.1)</td><td>13 (0.1)<br>1.3 (0.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.097</td></tr><tr><td rowspan="2">Volumetric scaling from t1 head image to standard space - visit 2, mean (SD)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Less than 14 weekly alcohol units</th><th>More than 14 weekly alcohol units</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td>Sample size</td><td>n</td><td></td><td>32498</td><td>21256</td><td>11242</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Outcome</td><td>G factor, mean (SD)</td><td></td><td>-0.0 (1.1)</td><td>0.0 (1.2)</td><td>-0.1 (1.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.140</td></tr><tr><td>Mediators</td><td>Dmri pc 0, mean (SD)</td><td>-0.3 (10.2)</td><td>-0.5 (10.2)</td><td>0.0 (10.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.050</td></tr><tr><td></td><td>Dmri pc 1, mean (SD)</td><td></td><td>0.1 (5.2)</td><td>0.5 (5.2)</td><td>-0.7 (5.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.229</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Less than 14 weekly alcohol units</th><th>More than 14 weekly alcohol units</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="14">Confounders (alphabetic order)</td><td>Dmri pc 2, mean (SD)</td><td rowspan="14">No</td><td>-0.1 (5.0)</td><td>-0.2 (5.1)</td><td>0.0 (4.9)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.043</td></tr><tr><td>Dmri pc 3, mean (SD)</td><td>0.0 (4.4)</td><td>-0.1 (4.4)</td><td>0.3 (4.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.097</td></tr><tr><td>Dmri pc 4, mean (SD)</td><td>0.0 (4.2)</td><td>-0.0 (4.3)</td><td>0.1 (4.2)</td><td>0.010</td><td>Two Sample T-test</td><td>0.030</td></tr><tr><td>Dmri pc 5, mean (SD)</td><td>0.0 (3.4)</td><td>-0.0 (3.4)</td><td>0.1 (3.4)</td><td>0.054</td><td>Two Sample T-test</td><td>0.022</td></tr><tr><td>Smri dmri pc 0, mean (SD)</td><td>-0.4 (10.5)</td><td>-0.4 (10.5)</td><td>-0.3 (10.6)</td><td>0.196</td><td>Two Sample T-test</td><td>0.015</td></tr><tr><td>Smri dmri pc 1, mean (SD)</td><td>-0.2 (7.4)</td><td>0.5 (7.4)</td><td>-1.5 (7.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.274</td></tr><tr><td>Smri dmri pc 2, mean (SD)</td><td>0.1 (5.6)</td><td>0.5 (5.5)</td><td>-0.6 (5.7)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.210</td></tr><tr><td>Smri dmri pc 3, mean (SD)</td><td>-0.0 (4.7)</td><td>-0.1 (4.8)</td><td>0.2 (4.5)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.079</td></tr><tr><td>Smri dmri pc 4, mean (SD)</td><td>-0.0 (4.3)</td><td>-0.1 (4.4)</td><td>0.1 (4.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.051</td></tr><tr><td>Smri dmri pc 5, mean (SD)</td><td>0.0 (4.3)</td><td>-0.0 (4.3)</td><td>0.2 (4.3)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.048</td></tr><tr><td>Smri pc 0, mean (SD)</td><td>0.3 (7.2)</td><td>-0.3 (7.1)</td><td>1.4 (7.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.241</td></tr><tr><td>Smri pc 1, mean (SD)</td><td>-0.0 (3.3)</td><td>-0.2 (3.3)</td><td>0.3 (3.4)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.146</td></tr><tr><td>Smri pc 2, mean (SD)</td><td>-0.1 (2.8)</td><td>-0.3 (2.8)</td><td>0.4 (2.8)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.249</td></tr><tr><td>Smri pc 3, mean (SD)</td><td>0.0 (2.1)</td><td>-0.0 (2.0)</td><td>0.1 (2.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.056</td></tr><tr><td>Adopted as a child - visit 0, n (%)</td><td>32469 (99.9)</td><td>21236 (99.9)</td><td>11233 (99.9)</td><td>0.908</td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.005</td></tr><tr><td>Age when attended assessment centre - visit 2, mean (SD)</td><td>Yes</td><td>9 (0.0)</td><td>6 (0.0)</td><td>3 (0.0)</td><td rowspan="2">0.245</td><td rowspan="2">Two Sample T-test</td><td rowspan="2">-0.013</td></tr><tr><td>Average total household income before tax - visit 2, n (%)</td><td>other</td><td>20 (0.1)</td><td>14 (0.1)</td><td>6 (0.1)</td></tr><tr><td></td><td>18,000 to 30,999</td><td>63.7 (7.6)</td><td>63.7 (7.7)</td><td>63.6 (7.4)</td><td></td><td>Chi-squared</td><td>0.263</td></tr><tr><td></td><td>31,000 to 51,999</td><td>9156 (28.2)</td><td>5823 (27.4)</td><td>3333 (29.6)</td><td rowspan="4">&lt;0.001</td><td rowspan="4">Two Sample T-test</td><td rowspan="4">0.087</td></tr><tr><td></td><td>52,000 to 100,000</td><td>7028 (21.6)</td><td>4226 (19.9)</td><td>2802 (24.9)</td></tr><tr><td></td><td>Do not know</td><td>961 (3.0)</td><td>739 (3.5)</td><td>222 (2.0)</td></tr><tr><td></td><td>Greater than 100,000</td><td>2277 (7.0)</td><td>1222 (5.7)</td><td>1055 (9.4)</td></tr><tr><td></td><td>Less than 18,000</td><td>3402 (10.5)</td><td>2536 (11.9)</td><td>866 (7.7)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.061</td></tr><tr><td></td><td>Prefer not to answer</td><td>1861 (5.7)</td><td>1347 (6.3)</td><td>514 (4.6)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.031</td></tr><tr><td>Body mass index (bmi) - visit 2, mean (SD)</td><td>Do not know</td><td>26.4 (4.3)</td><td>26.3 (4.5)</td><td>26.7 (4.0)</td><td></td><td>Chi-squared</td><td>0.031</td></tr><tr><td>Breastfed as a baby - visit 0, n (%)</td><td>Do not know</td><td>6175 (19.0)</td><td>3882 (18.3)</td><td>2293 (20.4)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.051</td></tr><tr><td>Cmdd final, n (%)</td><td>No</td><td>7174 (22.1)</td><td>4819 (22.7)</td><td>2355 (20.9)</td><td rowspan="2">0.008</td><td rowspan="2">Chi-squared</td><td rowspan="2">0.034</td></tr><tr><td>Comparative body size at age 10 - visit 0, n (%)</td><td>Yes</td><td>19136 (58.9)</td><td>12547 (59.0)</td><td>6589 (58.6)</td></tr><tr><td></td><td>other</td><td>13 (0.0)</td><td>8 (0.0)</td><td>5 (0.0)</td><td></td><td>Chi-squared</td><td>0.034</td></tr><tr><td></td><td>False</td><td>23413 (72.0)</td><td>15211 (71.6)</td><td>8202 (73.0)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.034</td></tr><tr><td></td><td>True</td><td>9085 (28.0)</td><td>6045 (28.4)</td><td>3040 (27.0)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.051</td></tr><tr><td></td><td>About average</td><td>16637 (51.2)</td><td>10863 (51.1)</td><td>5774 (51.4)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.034</td></tr><tr><td>Comparative height size at age 10 - visit 0, n (%)</td><td>Do not know</td><td>347 (1.1)</td><td>242 (1.1)</td><td>105 (0.9)</td><td rowspan="4">0.089</td><td rowspan="4">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="4">0.034</td></tr><tr><td></td><td>Plumper</td><td>4922 (15.1)</td><td>3329 (15.7)</td><td>1593 (14.2)</td></tr><tr><td></td><td>Thinner</td><td>10584 (32.6)</td><td>6816 (32.1)</td><td>3768 (33.5)</td></tr><tr><td></td><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.0)</td></tr><tr><td></td><td>About average</td><td>17039 (52.4)</td><td>11119 (52.3)</td><td>5920 (52.7)</td><td></td><td>Chi-squared (warning: expected count &lt; 5)</td><td>0.034</td></tr><tr><td>Country of birth (uk/elsewhere) - visit 0, n (%)</td><td>Do not know</td><td>293 (0.9)</td><td>212 (1.0)</td><td>81 (0.7)</td><td rowspan="5">&lt;0.001</td><td rowspan="5">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="5">0.127</td></tr><tr><td></td><td>Shorter</td><td>6569 (20.2)</td><td>4332 (20.4)</td><td>2237 (19.9)</td></tr><tr><td></td><td>Taller</td><td>8589 (26.4)</td><td>5587 (26.3)</td><td>3002 (26.7)</td></tr><tr><td></td><td>other</td><td>8 (0.0)</td><td>6 (0.0)</td><td>2 (0.0)</td></tr><tr><td></td><td>Elsewhere</td><td>1778 (5.5)</td><td>1360 (6.4)</td><td>418 (3.7)</td></tr><tr><td></td><td>England</td><td>27360 (84.2)</td><td>17747 (83.5)</td><td>9613 (85.5)</td><td rowspan="6">&lt;0.001</td><td rowspan="6">Chi-squared (warning: expected count &lt; 5)</td><td rowspan="6">0.127</td></tr><tr><td></td><td>Northern Ireland</td><td>234 (0.7)</td><td>133 (0.6)</td><td>101 (0.9)</td></tr><tr><td></td><td>Republic of Ireland</td><td>217 (0.7)</td><td>137 (0.6)</td><td>80 (0.7)</td></tr><tr><td></td><td>Scotland</td><td>2296 (7.1)</td><td>1482 (7.0)</td><td>814 (7.2)</td></tr><tr><td></td><td>Wales</td><td>600 (1.8)</td><td>387 (1.8)</td><td>213 (1.9)</td></tr><tr><td></td><td>other</td><td>13 (0.0)</td><td>10 (0.0)</td><td>3 (0.0)</td></tr></tbody></table>
...continued

<table><thead><tr><th>variable role</th><th>variable name</th><th>variable modalities</th><th>Overall</th><th>Less than 14 weekly alcohol units</th><th>More than 14 weekly alcohol units</th><th>P-Value</th><th>Test</th><th>SMD (0,1)</th></tr></thead><tbody><tr><td rowspan="14"></td><td>Current employment status - visit 2, n (%)</td><td>In paid employment or self-employed</td><td>12978 (39.9)</td><td>8486 (39.9)</td><td>4492 (40.0)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.069</td></tr><tr><td rowspan="2">Current smoker, n (%)</td><td>Retired</td><td>18302 (56.3)</td><td>11880 (55.9)</td><td>6422 (57.1)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>1218 (3.7)</td><td>890 (4.2)</td><td>328 (2.9)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Current tobacco smoking - visit 2, n (%)</td><td>0</td><td>31893 (98.1)</td><td>20926 (98.4)</td><td>10967 (97.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.064</td></tr><tr><td>1</td><td>605 (1.9)</td><td>330 (1.6)</td><td>275 (2.4)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Diabetic, n (%)</td><td>No</td><td>31431 (96.7)</td><td>20720 (97.5)</td><td>10711 (95.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.123</td></tr><tr><td>Yes, on most or all days other</td><td>605 (1.9)</td><td>330 (1.6)</td><td>275 (2.4)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Ethnic background - visit 2, n (%)</td><td>0</td><td>462 (1.4)</td><td>206 (1.0)</td><td>256 (2.3)</td><td></td><td></td><td></td></tr><tr><td>1</td><td>31154 (95.9)</td><td>20335 (95.7)</td><td>10819 (96.2)</td><td>0.015</td><td>Chi-squared</td><td>0.029</td></tr><tr><td rowspan="2">Ever smoked - visit 2, n (%)</td><td>British</td><td>1344 (4.1)</td><td>921 (4.3)</td><td>423 (3.8)</td><td>0.011</td><td>Chi-squared</td><td>0.030</td></tr><tr><td>other</td><td>7408 (22.8)</td><td>4753 (22.4)</td><td>2655 (23.6)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Handedness (chirality/laterality) - visit 0, n (%)</td><td>No</td><td>25090 (77.2)</td><td>16503 (77.6)</td><td>8587 (76.4)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.347</td></tr><tr><td>Yes</td><td>15217 (46.8)</td><td>11201 (52.7)</td><td>4016 (35.7)</td><td></td><td></td><td></td></tr><tr><td rowspan="2"></td><td>other</td><td>17196 (52.9)</td><td>10001 (47.1)</td><td>7195 (64.0)</td><td></td><td></td><td></td></tr><tr><td>Left-handed</td><td>85 (0.3)</td><td>54 (0.3)</td><td>31 (0.3)</td><td></td><td></td><td></td></tr><tr><td rowspan="2"></td><td rowspan="2"></td><td>Right-handed</td><td>28957 (89.1)</td><td>18962 (89.2)</td><td>9995 (88.9)</td><td></td><td></td><td></td></tr><tr><td>Use both right and left hands equally</td><td>486 (1.5)</td><td>325 (1.5)</td><td>161 (1.4)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Hypercholesterol, n (%)</td><td>0</td><td>12 (0.0)</td><td>9 (0.0)</td><td>3 (0.0)</td><td></td><td></td><td></td></tr><tr><td>1</td><td>24538 (75.5)</td><td>16341 (76.9)</td><td>8197 (72.9)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.091</td></tr><tr><td rowspan="2">Hypertensive, n (%)</td><td>0</td><td>7960 (24.5)</td><td>4915 (23.1)</td><td>3045 (27.1)</td><td></td><td></td><td></td></tr><tr><td>1</td><td>23962 (73.7)</td><td>15968 (75.1)</td><td>7994 (71.1)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.091</td></tr><tr><td rowspan="2">Inflammation, n (%)</td><td>False</td><td>8536 (26.3)</td><td>5288 (24.9)</td><td>3248 (28.9)</td><td></td><td></td><td></td></tr><tr><td>True</td><td>27267 (83.9)</td><td>17639 (83.0)</td><td>9628 (85.6)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.073</td></tr><tr><td rowspan="3">Job involves shift work - visit 2, n (%)</td><td>Always</td><td>5231 (16.1)</td><td>3617 (17.0)</td><td>1614 (14.4)</td><td></td><td></td><td></td></tr><tr><td>Never/rarely</td><td>795 (2.4)</td><td>538 (2.5)</td><td>257 (2.3)</td><td>0.357</td><td>Chi-squared</td><td>0.021</td></tr><tr><td>Sometimes other</td><td>11077 (34.1)</td><td>7219 (34.0)</td><td>3858 (34.3)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Length of time at current address - visit 2, mean (SD)</td><td>0</td><td>19771 (60.8)</td><td>545 (2.6)</td><td>310 (2.8)</td><td></td><td></td><td></td></tr><tr><td>1</td><td>21.0 (13.9)</td><td>12954 (60.9)</td><td>6817 (60.6)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Life long depression, n (%)</td><td>False</td><td>27461 (84.5)</td><td>17744 (83.5)</td><td>9717 (86.4)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.083</td></tr><tr><td>True</td><td>5037 (15.5)</td><td>3512 (16.5)</td><td>1525 (13.6)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Ls pc dim.1, mean (SD)</td><td>0</td><td>0.6 (2.0)</td><td>0.5 (2.1)</td><td>0.9 (2.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.200</td></tr><tr><td>1</td><td>-0.4 (2.0)</td><td>-0.3 (2.0)</td><td>-0.8 (2.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.268</td></tr><tr><td rowspan="2">Ls pc dim.2, mean (SD)</td><td>0</td><td>3388 (10.4)</td><td>2180 (10.3)</td><td>1208 (10.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.093</td></tr><tr><td>1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Maternal smoking around birth - visit 0, n (%)</td><td>Do not know</td><td>20344 (62.6)</td><td>13624 (64.1)</td><td>6720 (59.8)</td><td></td><td></td><td></td></tr><tr><td>False</td><td>8749 (26.9)</td><td>5440 (25.6)</td><td>3309 (29.4)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Mh pc dim.1, mean (SD)</td><td>Yes</td><td>17 (0.1)</td><td>12 (0.1)</td><td>5 (0.0)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>1.0 (6.5)</td><td>0.8 (6.6)</td><td>1.4 (6.5)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.102</td></tr><tr><td rowspan="2">Mh pc dim.2, mean (SD)</td><td>0</td><td>0.5 (3.3)</td><td>0.2 (3.3)</td><td>1.0 (3.2)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.255</td></tr><tr><td>1</td><td>2.2 (1.0)</td><td>2.1 (1.0)</td><td>2.2 (1.0)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>0.054</td></tr><tr><td rowspan="2">Number in household - visit 2, mean (SD)</td><td>0</td><td>1.0 (1.1)</td><td>1.1 (1.1)</td><td>1.0 (1.1)</td><td>&lt;0.001</td><td>Two Sample T-test</td><td>-0.047</td></tr><tr><td>1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Number of full brothers - visit 2, mean (SD)</td><td>Four or more</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>1.0 (1.1)</td><td>0.516</td><td>Two Sample T-test</td><td>-0.008</td></tr><tr><td>False</td><td>922 (2.8)</td><td>555 (2.6)</td><td>367 (3.3)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.131</td></tr><tr><td rowspan="5">Obesity, n (%)</td><td>None</td><td>1265 (3.9)</td><td>925 (4.4)</td><td>340 (3.0)</td><td></td><td></td><td></td></tr><tr><td>One</td><td>13770 (42.4)</td><td>9329 (43.9)</td><td>4441 (39.5)</td><td></td><td></td><td></td></tr><tr><td>Three</td><td>3034 (9.3)</td><td>1860 (8.8)</td><td>1174 (10.4)</td><td></td><td></td><td></td></tr><tr><td>Two other</td><td>13471 (41.5)</td><td>8558 (40.3)</td><td>4913 (43.7)</td><td></td><td></td><td></td></tr><tr><td>0</td><td>36 (0.1)</td><td>29 (0.1)</td><td>7 (0.1)</td><td></td><td></td><td></td></tr><tr><td rowspan="2">Part of a multiple birth - visit 0, n (%)</td><td>0</td><td>26781 (82.4)</td><td>17509 (82.4)</td><td>9272 (82.5)</td><td>0.826</td><td>Chi-squared</td><td>0.003</td></tr><tr><td>1</td><td>5717 (17.6)</td><td>3747 (17.6)</td><td>1970 (17.5)</td><td></td><td></td><td></td></tr><tr><td rowspan="3">Past tobacco smoking - visit 2, n (%)</td><td>No</td><td>31809 (97.9)</td><td>20795 (97.8)</td><td>11014 (98.0)</td><td>0.704</td><td>Chi-squared</td><td>0.010</td></tr><tr><td>Yes</td><td>644 (2.0)</td><td>431 (2.0)</td><td>213 (1.9)</td><td></td><td></td><td></td></tr><tr><td>other</td><td>45 (0.1)</td><td>30 (0.1)</td><td>15 (0.1)</td><td></td><td></td><td></td></tr><tr><td></td><td>I have never smoked</td><td>15218 (46.8)</td><td>11202 (52.7)</td><td>4016 (35.7)</td><td>&lt;0.001</td><td>Chi-squared</td><td>0.398</td></tr></tbody></table>