An obesity genetic risk score predicts risk of insulin resistance among Chinese children.

A great number of body mass index (BMI)/obesity-related loci have been identified by recent genome-wide association studies. The objective of the study is to investigate the associations of 11 obesity-related loci with insulin resistance (IR) in a Chinese children population. Participants included 3,468 Chinese children, aged 6-18 years. The 75 percentile (equal to 2.93) of homeostasis model assessment of IR (HOMA-IR) index was considered as the cut-off of IR. A total of 868 IR cases and 2,600 control children were identified. In age- and sex-adjusted model, only two SNPs in/near GNPDA2 and KCTD15 genes were significantly associated with risk of IR [GNPDA2 rs10938397: allelic odds ratio (OR) = 1.19, 95 % confidence interval (CI) 1.06-1.34, P = 0.003; KCTD15 rs29941: allelic OR = 1.15, 95 % CI = 1.01-1.31, P = 0.034]; genetic risk score was also significantly associated risk of IR (OR = 1.08, 95 % 1.04-1.12, P = 1.18 × 10(-4)). After additional adjustment for BMI, none remained significant. The associations of GNPDA2 rs10938397 and the SNPs in combination with risk of IR remained statistically significant after correction for multiple testing. The present study demonstrated that the associations of GNPDA2 rs10938397 and the SNPs in combination with risk of IR were statistically significant, which were dependent on BMI.