Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s

BACKGROUND: Genome‐wide association studies have identified loci that significantly increase diabetes risk. This study explored the genetic susceptibility in relation to diabetes risk in adulthood among a Chinese population born in the early 1960s. METHODS: In all, 2129 subjects (833 males, 1296 females) were selected from the cross‐sectional 2010 to 2012 China National Nutrition and Health Survey. Fifty diabetes‐related single nucleotide polymorphisms (SNPs) were detected. Two diabetes genetic risk scores (GRSs) based on the 50 diabetes‐predisposing variants were developed to examine the association of these SNPs with diabetes risk. RESULTS: Associations were found between diabetes risk and SNPs in the MTNR1B (rs10830963), KLHDC5 (rs10842994), GRK5 (rs10886471), cyclindependentkinase 5 regulatory subunit associated protein 1 (rs10946398), adaptorrelated protein complex 3 subunit sigma 2 (rs2028299), diacylglycerol kinase beta/transmembrane protein 195 (rs2191349), SREBF chaperone (rs4858889), ankyrin1 (rs516946), RAS guanyl releasing protein 1 (rs7403531), and zinc finger AN1‐type containing 3 (rs9470794) genes. As a continuous variable, with a 1‐point increase in the GRS or weighted (w) GRS, fasting plasma glucose (FPG) increased 0.045 and 0.044 mM, respectively (P < 0.001 for both), after adjusting for confounders. Both GRS and wGRS showed an association with diabetes, with a multivariable‐adjusted odds ratio (95% confidence interval) of 1.09 (1.00‐1.19) and 1.12 (1.03‐1.22), respectively, among all subjects. No significant associations were found between the GRS or wGRS and impaired fasting glucose or impaired glucose tolerance. CONCLUSIONS: The data suggest the association of 10 SNPs and the GRS or wGRS with diabetes risk. Genetic susceptibility to diabetes may synergistically affect the risk of diabetes in adulthood.