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

目的：很少有前瞻性研究研究来自糖尿病GWAS的SNPs与普通人群糖尿病发病率之间的关联。方法：对2,231名40岁及以上的日本社区居民进行了为期7年的随访。在随访期间，228名受试者被诊断为新糖尿病。结果如下：在CDKAL 1、CDKN 2A/2B、DCD、FTO、KCNQ 1和HNF 4A基因上具有SNP的受试者中，发生糖尿病的年龄和性别校正风险比（HR）显著较高。当根据6个基因中风险多态性的数量分为4组，即0-4、5、6、7和更多时，与具有0-4个风险多态性的个体相比，如果受试者具有5个和更多风险多态性，则糖尿病发展的多变量调整HR显著增加（6个风险多态性：校正的HR=1.8：6个风险多态性：校正的HR=2.0：7和更多风险多态性：校正的HR=3.1）。通过将风险多态性的数量添加到包括其他潜在风险因素的模型（0.732）中，与仅添加其他潜在风险因素（0.706）相比，受试者工作特征曲线下面积显著增加（面积差异p =0.008）。总之，风险多态性的数量是糖尿病发展的一个重要危险因素。

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.