382 ALOX12 polymorphisms are associated with fat mass in men W-J Xiao et al GGGAG and GGAGA) accounted for 91.8% of the unrelated parents. Association of the peak BMD and obesity phenotypes with SNPs in nuclear families ANOVA and QTDT analyses. Using 400 nuclear families has a power of 480% to test a candidate gene as a QTL, which can explain B10% of the variation in the BMD or obesity phenotypes. We investigated the association of the SNP genotypes with the BMD and obesity phenotypes using ANOVA in 400 unrelated sons randomly selected from 415 sons. Two SNPs (rs2073438 and rs312462) showed significant association with the TFM and PFM (Po0.05). The sons with the AA genotype at rs2073438 had a higher adjusted TFM (P ¼ 0.001) and a higher PFM (P ¼ 0.014) compared with the GG genotype. This SNP contributed to 3.8 and 2.6% of the FM and PFM variation, respectively, in our sample. Indivi- duals carrying the GG genotype at rs312462 had a higher TFM and PFM compared with GA carriers (P ¼ 0.011 and 0.003, respectively). The contributions of rs312462 to the phenotypic variation of TFM and PFM were 3.0 and 3.7%, Genotype rs2073438 GG AG AA P-value rs2292350 GG AG AA P-value rs312470 AA AG GG P-value rs434473 AA AG GG P-value rs312462 GG GA AA P-value n 173 180 47 168 183 49 278 111 11 104 210 86 287 103 10 International Journal of Obesity respectively. However, no significant association was found between any SNP and the BMD, BMI or TLM variation in young men (Table 5). The associations among the peak BMD, obesity pheno- types and SNPs in ALOX12 were analyzed using the QTDT for our nuclear families. As the effects of parent phenotypes were excluded in the analyses, all 400 families were included. There were 284, 273, 195, 310 and 189 informative families for the TDT analysis at rs2073438, rs2292350, rs312470, rs434473 and rs312462, respectively. We did not detect significant population stratification in our sample. The SNPs rs2073438 and rs312462 were significantly associated with the TFM and PFM in the total-association analysis (Po0.01). For the within-family analysis, significant associations were found between rs2073438 and the TFM, PFM and BMI (P ¼ 0.007, 0.012 and 0.038, respectively), whereas rs312462 showed only marginal association with the TFM (P ¼ 0.049). In the multiple parameters tests, permutations of 1000 tests were performed. However, only rs2073438 retained signifi- cant with-family associations with both the TFM and the PFM (P ¼ 0.033 and 0.015, respectively). Similar to the results of the ANOVA, we failed to find significant associations BMI (kg m–2) 23.5±3.5 23.7±3.3 24.1±3.1 0.597 23.7±3.3 23.8±3.5 22.8±2.6 0.171 23.5±3.2 23.9±3.6 24.8±3.4 0.180 23.7±3.3 23.6±3.3 23.8±3.6 0.874 23.9±3.3 23.2±3.3 22.1±3.8 0.632 TFM (kg) PFM (%) TLM (kg) 15.06±6.83 16.32±6.85 18.37±6.93# 0.001 16.49±7.98 16.06±7.11 15.10±6.42 0.598 16.23±7.87 16.14±6.41 14.12±5.82 0.731 15.69±6.88 15.85±6.85 17.45±9.19 0.203 16.93±7.61 14.26±6.69* 13.54±6.88 0.003 20.90±7.01 22.13±7.15 24.46±6.67## 0.015 21.94±6.99 21.99±7.38 21.16±7.18 0.843 21.83±7.53 22.18±6.36 20.28±6.41 0.768 21.66±6.92 21.74±7.22 22.57±7.42 0.608 22.67±7.01 19.62±7.01** 24.10±4.36 0.001 51.15±5.32 51.37±5.99 50.96±5.33 0.918 51.47±5.45 51.06±5.86 51.01±5.32 0.807 51.31±5.54 51.06±5.82 50.97±3.21 0.925 50.98±5.88 51.25±5.55 51.47±5.57 0.822 51.06±5.71 51.70±5.52 50.51±3.21 0.570 Abbreviations: BMD, bone mineral density; BMI, body mass index; PFM, percentage fat mass; SNP, single-nucleotide polymorphism; TFM, total fat mass; TLM, total lean mass. The P-values are the results of analysis of variance (ANOVA) tests for the least-square mean of the BMD among various genotypes after adjusting for the significant covariates of age, weight and height. The P-values are the results of ANOVA tests for the least-square mean of the BMI, TFM and TLM among various genotypes after adjusting for age as a significant covariate. Bold indicates significant P-values (Po0.05). #P ¼ 0.001, AA genotype versus GG genotype; ##P ¼ 0.014, AA genotype versus GG genotype; *P ¼ 0.011, GG genotype versus GA genotype; **P ¼ 0.003, GG genotype versus GA genotype. Table 5 Association of SNPs with phenotypic values in unrelated sons from single-offspring families (mean±s.d.) Lumbar spine BMD (g cm–2) 1.140±0.142 1.121±0.132 1.184±0.136 0.076 1.139±0.139 1.140±0.133 1.124±0.150 0.857 1.138±0.137 1.146±0.139 1.138±0.137 0.803 1.138±0.147 1.135±0.132 1.156±±0.138 0.560 1.145±0.140 1.122±0.126 1.123±0.178 0.234 Femoral neck BMD (g cm–2) 1.002±0.137 0.995±0.149 0.983±0.137 0.579 0.994±0.139 1.000±0.148 0.989±0.119 0.802 0.994±0.139 1.003±0.149 0.994±0.139 0.532 1.001±0.139 0.999±0.144 0.987±0.144 0.519 0.998±0.145 0.985±0.135 1.107±0.117 0.254 Total hip BMD (g cm–2) 1.018±0.137 1.013±0.143 1.019±0.124 0.696 1.017±0.131 1.020±0.149 0.986±0.107 0.592 1.011±0.132 1.026±0.150 1.011±0.132 0.469 1.007±0.140 1.016±0.136 1.014±0.138 0.535 1.016±0.139 1.010±0.134 1.161±0.139 0.144