Abstract

BackgroundGenome‐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.MethodsIn 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.ResultsAssociations 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.ConclusionsThe 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.

Highlights

  • Diabetes is a serious public health problem

  • This study explored the genetic susceptibility in relation to diabetes risk in adulthood among a Chinese population born in the early 1960s

  • Associations were found between diabetes risk and single nucleotide polymorphisms (SNPs) in the melatonin receptor 1B (MTNR1B), kelchdomain containing 5 (KLHDC5), Gprotein-coupled receptor kinase 5 (GRK5), cyclindependentkinase 5 regulatory subunit associated protein 1, adaptorrelated protein complex 3 subunit sigma 2, diacylglycerol kinase beta/transmembrane protein 195, SREBF chaperone, ankyrin[1], RAS guanyl releasing protein 1, and zinc finger AN1-type containing 3 genes

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Summary

| INTRODUCTION

Diabetes is a serious public health problem. The number of cases and the prevalence of diabetes have been steadily increasing over the past few decades. An estimated 422 million adults were living with diabetes in 2014.1 According to the Report on Chinese Residents' Chronic Disease and Nutrition (2015),[2] the prevalence of diabetes among Chinese adults aged 18 years or older had increased from 4.2% in 2002 to 9.7% in 2012. Environmental factors such as diet and lifestyle have clearly contributed to the recent rise in the prevalence of diabetes, there is increasing evidence that common variants in the human genome contribute to the development of diabetes.[3–7]. In this study we used data from the China National Nutrition and Health Survey (CNNHS) 2010 to 2012 to evaluate genetic susceptibility by combining the 61 SNPs identified from recent GWAS.[6,9–12]

| METHODS
| RESULTS
Findings
| DISCUSSION
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