Gene-environment correlations across geographic regions affect genome-wide association studies.
Gene-environment correlations across geographic regions affect genome-wide association studies.
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DOI：
10.1038/s41588-022-01158-0
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发表时间：
2022-09
期刊：
影响因子：
30.8
通讯作者：
Nivard, Michel G.
中科院分区：
文献类型：
--
作者：
Abdellaoui, Abdel;Dolan, Conor, V;Verweij, Karin J. H.;Nivard, Michel G.
在全基因组关联研究（GWASs）中，基因-环境相关性影响遗传变异和复杂性状之间的关联。在这里，我们在多达43，516名英国兄弟姐妹中显示，教育程度多基因得分捕获了基因-环境相关性，并且移民将这些基因-环境相关性扩展到家庭以外的更广泛的地理区域。然后，我们对多达254，387名英国人的56个复杂特征进行了GWAS。控制地理区域显着降低了社会经济地位（SES）相关性状的遗传力，最强烈的教育程度和收入。对于大多数性状，控制区域显着降低了与教育程度和收入的遗传相关性，最显着的是体重指数/体脂，久坐行为和物质使用，与区域社会经济差异相关的基因-环境相关性一致。控制出生地和当前地址的影响表明基因-环境相关性的被动和主动来源。我们的研究结果表明，DNA和SES的地理聚类引入了影响GWAS结果的基因-环境相关性。对英国生物库中56个复杂性状的地理区域的基因-环境相关性分析表明，基因-环境相关性的被动和主动来源都会影响遗传关联信号。
Gene–environment correlations affect associations between genetic variants and complex traits in genome-wide association studies (GWASs). Here we showed in up to 43,516 British siblings that educational attainment polygenic scores capture gene–environment correlations, and that migration extends these gene–environment correlations beyond the family to broader geographic regions. We then ran GWASs on 56 complex traits in up to 254,387 British individuals. Controlling for geographic regions significantly decreased the heritability for socioeconomic status (SES)-related traits, most strongly for educational attainment and income. For most traits, controlling for regions significantly reduced genetic correlations with educational attainment and income, most significantly for body mass index/body fat, sedentary behavior and substance use, consistent with gene–environment correlations related to regional socio-economic differences. The effects of controlling for birthplace and current address suggest both passive and active sources of gene–environment correlations. Our results show that the geographic clustering of DNA and SES introduces gene–environment correlations that affect GWAS results. Analyses of gene–environment correlations across geographic regions for 56 complex traits in UK Biobank suggest that both passive and active sources of gene–environment correlation affect genetic association signals.
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