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Two novel susceptibility loci for type 2 diabetes mellitus identified by longitudinal exome-wide association studies in a Japanese population

机译：日本人口纵向外界协会研究鉴定的两种新的易感性位点鉴定了2型糖尿病

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Recent genome-wide association studies identified genetic variants that confer susceptibility to type 2 diabetes mellitus (T2DM). However, few longitudinal genome-wide association studies of this metabolic disorder have been reported to date. Therefore, we performed a longitudinal exome-wide association study of T2DM, using 24,579 single nucleotide polymorphisms (SNPs) and repeated measurements from 6022 Japanese individuals. The generalized estimating equation model was applied to test relations of SNPs to three T2DM-related parameters: prevalence of T2DM, fasting plasma glucose level, and blood glycosylated hemoglobin content. Three SNPs that passed quality control were significantly (P 2.26 x 10(-7)) associated with two of the three T2DM-related parameters in additive and recessive models. Of the three SNPs, rS6414624 in EVC and rS78338345 in GGA3 were novel susceptibility loci for T2DM. In the present study, the SNP of GGA3 was predicted to be a genetic variant whose minor allele frequency has recently increased in East Asia.
机译：最近的基因组关联研究确定了赋予2型糖尿病（T2DM）易感性的遗传变异。然而，迄今为止据报道，少量对这种代谢疾病的纵向基因组关联研究。因此，我们使用24,579个单核苷酸多态性（SNP）进行了T2DM的纵向稀有关联研究，并重复测量来自6022个日本人。将广义估计方程模型应用于测试SNP与三个T2DM相关参数的关系：T2DM的患病率，空腹血浆水平和血液糖基血红蛋白含量。通过质量控制的三个SNP显着（P <2.26×10（-7））与添加剂和隐性模型中的三个T2DM相关参数中的两种相关联。在三个SNP中，GGA3中的EVC和RS78338345的RS6414624是T2DM的新型易感位点。在本研究中，预计GGA3的SNP是一种遗传变异，其次要的等位基因频率最近在东亚增加。

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