SNPs drived form diabetes GWAS and incidence of diabetes in a general population : the Hisayama Study

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Objective : Few prospective studies have examined the association between SNPs derived form GWAS of diabetes and the incidence of diabetes in general populations. Methods : A total of 2,231 community-dwelling Japanese individuals aged 40 and more without diabetes were followed up for 7 years. During the follow-up, 228 subjects was diagnosed newly diabetes. Results : The age- and sex-adjusted hazard ratios (HRs) for the development of diabetes was significantly higher in subjects with the SNPs on the CDKAL1, CDKN2A/2B, DCD, FTO, KCNQ1 and HNF4A genes. When divided into four groups, namely 0-4, 5, 6, 7 and more, according to the number of risk polymorphisms in the six genes, the multivariable adjusted-HRs for the development of diabetes significantly increased if subjects had five and more risk polymorphisms compared to individuals who had 0-4 risk polymorphisms (6 risk polymorphisms : adjusted HR=1.8:6 risk polymorphisms : adjusted HR=2.0:7 and more risk polymorphisms : adjusted HR=3.1). The area under the receiver operating characteristic curve significantly increased by adding the number of risk polymorphisms to the model including other potential risk factors (0.732)compared with those of other potential risk factors only (0.706) (p for difference in the area=0.008). In conclusion, the number of risk polymorphisms was a significant risk factor for the development of diabetes.