Spreadsheet: ce6d226a-1270-417c-a05a-e6d9363a7d40
Sheet: Sheet1

Study characteristics and details of analysis metrics and methods | Unnamed: 1 | Unnamed: 2 | Unnamed: 3 | Unnamed: 4 | Unnamed: 5 | Unnamed: 6 | Unnamed: 7 | Unnamed: 8 | Unnamed: 9 | Unnamed: 10 | Unnamed: 11
 | COHORT | Steno | DCCT/EDIC (*) | FinnDiane - R | France | Italy | Romania | Karolinska | Umeå/Sweden | Diabetes Registry Scania | UK - Rep
COHORT INFORMATION | Contact person | [NAME] | [NAME] | [NAME] | Samy HADJADJ | Gianpaolo Zerbini | Nicolae Mircea PANDURU | [NAME] | [NAME] | [NAME] | AJ McKnight
 | Ethnicity | European | European | Finnish | European | European | European | Swedish | Swedish | Scandinavian | European
 | Country | Denmark | Canada and US | Finland | France, Belgium | Italy | Romania | Sweden | Sweden | Sweden | UK-ROI
 | Ethics approval date |  | 2010-11-01 00:00:00 | 2007-10-01 00:00:00 | 1998-09-18 00:00:00 | 1994-04-14 00:00:00 | 1/15/2009 and 10/10/2010 | 5/13/1997 and 2/4/2002 |  | 4/14/1999
 | Collection type | Case/control with follow-up data | clinical trial | Nationwide multicenter study | case/control | Case/control | Case/Control | Case/control | Case/control | Cohort | Case/Control
CONTROLS | N (M/F) | 197/178 |  | 139/145 | 222/225 | 99/86 | 30/34 | 103/108 | 73/66 | 158/132 | 225/222
 | Age                                                                   [Mean (SD) M/F], years | 50 (11.8)/51 (11.1) |  | 39 (12.5)/40 (12.7) | 43 (11.9)/45 (11.7) | 34 (9.4)/37 (11.5) | 44 (12.3)/48 (15.2) | 46 (11.8)/46 (12.1) | 48 (10.3)/46 (10.3) | 38 (11.1)/41 (15.2) | 61 (13.6)/58 (16.6)
 | BMI                                                                   [Mean (SD) M/F], kg/ m2 | 25 (3.2)/25 (4.0) |  | 25 (3.42)/25 (4.7) | 25 (2.8)/24 (3.6) | 24 (3.7)/ 23 (3.4) | 24 (3.3)/25.19 (3.8) | 25 (2.4)/25 (3.6) | 25 (2.1)/24 (3.6) | 24 (2.6)/24 (3.4) | 26 (3.5)/25 (3.8)
 | Serum creatinine                                                                   [Mean (SD) M/F], mg/dl | 1.0 (0.1)/1.0 (0.2) |  | 0.9 (0.1)/0.7 (0.2) | 0.9 (0.2)/0.8 (0.3) | 0.9 (0.1)/0.8 (0.2) | 0.8 (0.1)/0.8 (0.2) | 0.8 (0.1)/0.7 (0.1) |  | 1.0 (0.1)/0.9 (0.1) | 1.2 (0.2)/1.1 (0.2)
 | DM duration                                                                    [Mean (SD) M/F], years | 33 (9.9)/34 (10.9) |  | 25 (9.3)/24 (10.0) | 28 (9.7)/29 (9.1) | 24 (6.4)/24 (7.7) | 23 (8.0)/26 (8.8) | 27 (10.2)/29 (10.4) | 32 (8.7)/34 (8.8) | 30 (10.4)/33 (13.8) | 46 (14.9)/44 (16.0)
 | Age of DM onset                                                                   [Mean (SD) M/F], years | 18 (8.8)/17 (8.6) |  | 14 (9.3)/16 (10.0) | 17 (9.3)/14 (8.0) | 10 (7.9)/12 (7.8) | 21 (11.4)/22 (12.5) | 18 (11.6)/11 (6.9) | 15 (7.5)/11 (8.1) | 18 (9.5)/17 (9.4) | 15 (7.3)/15 (8.4)
 | HbA1c                                                                  [Mean (SD) M/F], % | 7.9 (1.1)/7.9 (1.1) |  | 8.3 (1.4)/8.4 (1.5) | 8.4 (1.5)/8.3 (1.2) | 8.6 (1.8) /8.3 (1.3) | 8.1(2.1)/8.7 (1.7) | 6.9 (1.1)/7.5 (1.2) | 7.0 (1.0)/6.9 (1.1) | 7.0 (1.1)/7.3 (1.2) | 7.9 (1.4)/8.1 (1.6)
 | Use of BP meds                                                               [% M/F] | 13.2/20.2 |  | 11.9/1.5 | 17/23 |  | 51.7/26.8 |  | 3.2/4.2
 | Use of lipid-lowering meds                                                               [% M/F] |  |  | 8.5/0.0 |  | 2.1/4.9 | 72.2/41.7
CASES | N (M/F) | 307/205 |  | 34/16 | 333/252 | 131/81 | 85/36 | 40/26 | 49/48 | 82/56 | 131/75
 | Age                                                                   [Mean (SD) M/F], years | 49 (10.1)/50 (10.8) |  | 45 (11.8)/39 (7.6) | 44 (11.2)/39 (11.2) | 43 (8.6)/41 (8.2) | 44 (9.4)/42 (11.9) | 52 (10.7)/48 (10.5) | 48 (11.3)/45 (8.9) | 46 (13.2)/43 (14.5) | 51  (10.7)/48 (12.0)
 | BMI                                                                   [Mean (SD) M/F], kg/ m2 | 25 (3.8)/24 (4.2) |  | 26 (2.5)/NA (NA) | 24 (3.3)/24 (3.8) | 23 (3.9)/ 22 (4.3) | 24 (3.3)/22 (6.7) | 26 (4.0)/26 (4.2) | 25 (3.4)/26 (4.2) | 24 (3.0)/24 (2.3) | 26 (4.9)/26(5.2)
 | Serum creatinine                                                                   [Mean (SD) M/F], mg/dl | 2.1 (1.8)/1.7 (1.2) |  | 1.7 (1.2)/NA (NA) | 1.9 (1.9)/1.5 (1.5) | 3.9 (3.7)/2.8 (2.7) | 2.6 (3.0)/2.7 (3.2) | 2.0 (1.3)/1.6 (1.0) |  | 1.6 (1.4)/1.4 (1.1) | 2.8 (2.6)/2.6 (2.6)
 | DM duration                                                                    [Mean (SD) M/F], years | 35 (9.2)/37 (9.3) |  | 29 (8.1)/28 (7.7) | 27 (9.0)/25 (9.4) | 30 (8.4)/29 (7.2) | 23 ([NAME] (8.1) | 34 (12.4)/32 (9.4) | 32 (12.4)/33 (10.0) | 32 (13.3)/35 (15.8) | 32 (11.2)/31 (12.4)
 | Age of DM onset                                                                   [Mean (SD) M/F], years | 14 (8.6)/13 (8.1) |  | 15 (8.9)/11 (5.1) | 17 (9.0)/14 (8.4) | 12 (7.0)/11 (6.0) | 22 (10.6)/22 (12.3) | 16 (10.5)/14 (9.8) | 14 (8.1 )/10 (6.2) | 17 (10.0)/13 (8.8) | 19 (10.1)/17 (10.1)
 | HbA1c                                                                  [Mean (SD) M/F], % | 8.6 (1.3)/8.6 (1.4) |  | 8.0 (0.9)/NA (NA) | 8.6 (1.6)/8.9 (1.8) | 7.5 (1.8)/7.5 (1.9) | 8.5(2.6)/7.7 (4.4) | 6.9 (1.5)/7.7 (1.5) | 7.0 (1.4)/7.5 (1.3) | 8.4 (1.5)/8.8 (1.6) | 9.2 (1.5)/9.2 (2.9)
 | Use of BP meds                                                               [% M/F] | 72.1/64.7 |  | 100/NA | 83/77 |  | 73.2/48.3 |  | 78.0/59.2
 | Use of lipid-lowering meds                                                               [% M/F] |  |  | 66.7/NA |  | 6.4/9.2 | 27.8/58.3
 | ESRD (dialysis or transplant)                                                               [% M/F] | 23.7/14.0 |  | 17.6/6.3 | 12.5/14.3 | 40.5/36.4 | 60.7/39.3 | 32.5/15.4 | 41.6/26.7 | 19.4/20.8 | 19.1/17.3
GENOTYPING | In silico/de novo | de novo | in silico | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo
 | Genotyping platform and SNP panel | Sequenom iPLEX | [NAME] GWAS | Sequenom iPLEX | Sequenom iPLEX | Sequenom iPLEX | Sequenom iPLEX | Sequenom iPLEX | Sequenom iPLEX | Sequenom iPLEX | Sequenom iPLEX
 | Genotyping center | Belfast | [NAME] | Belfast | Cambridge, [NAME] | Belfast | Belfast | Belfast | Belfast | Lund | Belfast/Cambridge, Ma
SAMPLE QC | Genotyping calling algorithm | Sequenom MassArray Typer | [NAME] | Sequenom MassArray Typer | Sequenom MassArray Typer | Sequenom MassArray Typer | Sequenom MassArray Typer | Sequenom [NAME]; Karolinska and Umeå samples analyzed jointly together; 132 samples genotyped from Karolinska; 236 samples genotyped from Umeå |  | Sequenom MassArray Typer | Sequenom MassArray Typer
 | Call rate                                                                [filter detail/ N individuals excluded] | 95%/30 | 99%/0 | 95%/24 | 95%/32 | 90%/28 | 95%/1 | 95%/9 |  | 94%/9 | 95%/46
 | Ethnic outliers/ other exclusions | 128/no phenotype data or phenotype did not meet the criteria | 60 | 10 samples: phenotype did not meet the criteria | 69 samples did not meet the phenotype criteria | - | 20 samples did not meet the phenotype inclusion criteria | 28 samples did not meet the phenotype inclusion criteria |  | - | 299 subjects had missing covariates
 | Cases/controls for analysis | 434 cases (84 ESRD), 368 controls, 58 micro |  | 26 DN cases, 254 controls | 348 DN (of which 71 ESRD), 192 micro, 391 controls | 164 DN (of which 124 ESRs), 167 Controls | 85 DN cases (of which 25 ESRD), 23 micro, 56 controls | 56 DN cases (17 ESRD); 92 micro; 183 controls |  | 138 DN cases (of which 35 ESRD), 91 micro, 290 controls | 106 DN Cases (30 ESRS), 350 Controls
SNP QC | MAF                                                                  [filter detail/ N SNPs excluded] | 1%/0 | 1%/0 | 1%/1 | 1%/0 | 1%/0 | 5%/1 | 1%/0 |  | 1%/0 | 1%/
 | HWE                                                                [filter detail/N SNPs excluded] | <10E-6/0 | <10E-5 | 0/0 | <10-E7/6 | <10E-6/0 | <10-E7/0 | <10-E7/0 |  | 0.001/0 | <10E-6/0
 | Call rate                                                                [filter detail/ N SNPs excluded] | 95%/4 | >99% | 95%/5 | 95%/0 | 95%/6 | 95%/5 | 95%/6 |  | 95%/4 | 95%/4
 | Other | 4 excluded for MAC in ESRD analysis |  | 17 excluded for MAC in Primary DN analysis; all excluded for MAC for ESRD analysis | 0 SNPs removed for MAC for DN; 8 SNPs removed for MAC<10 for ESRD | - | 5 removed for MAC<10 for DN; 12 removed for MAC<10 for ESRD | 6 SNPs removed fro MAC < 10 for DN; 19 SNPs removed for MAC < 10 for ESRD |  |  | -
 | SNP number in QC'd dataset | 36/DN; 32/ESRD | 35 | 17 | 35/DN, 27/ESRD | 34 | 30/DN; 23/ESRD | 28/DN; 15/ESRD |  | 36 | 34
IMPUTATION          (if GWAS) | Imputation software |  | MACH
 | Imputation quality metrics
 | Other SNP QC filters applied?
DATA ANALYSIS | Adjustments | Age, sex, duration | stratify by year of entry, covariates: cohort, treatment, cohort*treatment interaction, sex, age, diabetes duration, hba1c, BMI, mean BP, triglycerides, hdl, total cholesterol, smoking, hypertension indicator | Age, sex, duration | Age, sex, duration | Age, sex, duration | Age, sex, duration | Age, Sex, Duration |  | Age, sex, T1D duration | Age, sex, duration
 | Analysis method | Logistic regression | cox PH | logistic regression | Logistic regression | Logistic Regression | Logistic regression | Logistic regression |  | Logistic regression | Logistic regression
 | Software for analysis | PLINK | SAS | PLINK | PLINK | Plink | PLINK | PLINK |  | STATA | PLINK
 | [NAME] (if GWAS)
 |  |  | (*) Because this cohort was analyzed as time-to-event, dichotomization of participants into cases and controls is not appropriate