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在 433,540 名东亚个体中鉴定 2 型糖尿病基因座。

Identification of type 2 diabetes loci in 433,540 East Asian individuals.

机构信息

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.

出版信息

Nature. 2020 Jun;582(7811):240-245. doi: 10.1038/s41586-020-2263-3. Epub 2020 May 6.

Abstract

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D); however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

摘要

全基因组关联研究 (GWAS) 的荟萃分析已经确定了 240 多个与 2 型糖尿病 (T2D) 相关的位点;然而,这些位点中的大多数是在对欧洲血统个体的分析中发现的。在这里,为了研究东亚个体的 T2D 风险,我们对 77418 名 T2D 患者和 356122 名健康对照个体的 GWAS 数据进行了荟萃分析。在主要分析中,我们在 183 个位点确定了 301 个不同的关联信号,并且在考虑和不考虑体重指数和性别的 T2D 关联模型中,我们确定了 61 个新的与 T2D 易感性相关的位点。在东亚和欧洲人群中与 T2D 相关的常见变异体显示出强烈相关的效应大小。以前未描述的关联包括在 GDAP1、PTF1A、SIX3、ALDH2 或附近、微小 RNA 簇以及影响肌肉和脂肪细胞分化的基因中的信号。在另一个位点,两个重叠的 T2D 信号处的表达数量性状基因座影响两个基因-NKX6-3 和 ANK1-在不同组织中。在不同人群中的关联研究确定了其他位点,并阐明了与疾病相关的基因、生物学和途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ba/7292783/2d0b9cac0b82/nihms-1570876-f0004.jpg

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