孟德尔随机化
遗传建筑学
生物
遗传力
遗传学
全基因组关联研究
计算生物学
遗传流行病学
数量性状位点
基因-环境相互作用
基因
进化生物学
遗传变异
单核苷酸多态性
基因型
作者
Xiaofeng Zhu,Yihe Yang,Noah Lorincz‐Comi,Gen Li,Amy R. Bentley,Paul S. de Vries,M. R. W. Brown,Alanna C. Morrison,Charles Rotimi,W. James Gauderman,D. C. Rao,Hugues Aschard
标识
DOI:10.1038/s41467-024-47806-3
摘要
Abstract There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. To address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci (6 independent signals) interacted with either cigarette smoking or alcohol consumption for serum lipids, and empirically demonstrate that interaction and mediation are the major contributors to genetic effect size heterogeneity across populations. The estimated lower bound of the interaction and environmentally mediated heritability is significant ( P < 0.02) for low-density lipoprotein cholesterol and triglycerides in Cross-Population data. Our study improves the understanding of the genetic architecture and environmental contributions to complex traits.
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