Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility.
Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility.
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DOI：
10.1038/ejhg.2016.17
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Morris AP
中科院分区：
文献类型：
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作者：
Cook JP;Morris AP
全基因组关联研究（GWAS）传统上是在来自同一祖先群体的同质人群中进行的。然而，随着GWAS在大规模多种族队列中的可用性越来越高，我们评估了一个用于检测遗传变异与复杂性状相关性的框架，允许人口结构，并开发了一个强大的测试祖先群体之间等位基因效应的异质性。我们应用GWAS数据从成人健康和老龄化遗传流行病学资源（一个大型多种族人群队列，用于调查年龄相关疾病的遗传和环境基础）中识别和分析与2型糖尿病（T2 D）易感性相关的基因座。我们确定了一个新的T2 D易感性基因座，其在全基因组范围内具有显著性（P<5 × 10−8），该基因座映射到TOMM 40-APOE，该区域先前与脂质代谢和阿尔茨海默病有关。我们还证实了以前的报告，在TCF 7 L2位点的单核苷酸多态性表现出最大程度的异质性，在种族群体之间的等位基因效应，与东亚血统的人群中观察到的风险最低。
Genome-wide association studies (GWAS) have traditionally been undertaken in homogeneous populations from the same ancestry group. However, with the increasing availability of GWAS in large-scale multi-ethnic cohorts, we have evaluated a framework for detecting association of genetic variants with complex traits, allowing for population structure, and developed a powerful test of heterogeneity in allelic effects between ancestry groups. We have applied the methodology to identify and characterise loci associated with susceptibility to type 2 diabetes (T2D) using GWAS data from the Resource for Genetic Epidemiology on Adult Health and Aging, a large multi-ethnic population-based cohort, created for investigating the genetic and environmental basis of age-related diseases. We identified a novel locus for T2D susceptibility at genome-wide significance (P<5 × 10−8) that maps to TOMM40-APOE, a region previously implicated in lipid metabolism and Alzheimer's disease. We have also confirmed previous reports that single-nucleotide polymorphisms at the TCF7L2 locus demonstrate the greatest extent of heterogeneity in allelic effects between ethnic groups, with the lowest risk observed in populations of East Asian ancestry.