Effects of variants of 50 genes on diabetes risk among Chinese population born in 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 0.044mM, 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.