全基因组关联研究
生命银行
人口分层
遗传关联
计算生物学
线性模型
比例(比率)
混合模型
人口
关联测试
基因-环境相互作用
生物
基因型
计算机科学
遗传学
统计
单核苷酸多态性
数学
医学
地图学
环境卫生
基因
地理
作者
Wujuan Zhong,Aparna Chhibber,Lan Luo,Devan V. Mehrotra,Judong Shen
摘要
Abstract Genotype-by-environment interaction (GEI or GxE) plays an important role in understanding complex human traits. However, it is usually challenging to detect GEI signals efficiently and accurately while adjusting for population stratification and sample relatedness in large-scale genome-wide association studies (GWAS). Here we propose a fast and powerful linear mixed model-based approach, fastGWA-GE, to test for GEI effect and G + GxE joint effect. Our extensive simulations show that fastGWA-GE outperforms other existing GEI test methods by controlling genomic inflation better, providing larger power and running hundreds to thousands of times faster. We performed a fastGWA-GE analysis of ~7.27 million variants on 452 249 individuals of European ancestry for 13 quantitative traits and five environment variables in the UK Biobank GWAS data and identified 96 significant signals (72 variants across 57 loci) with GEI test P-values < 1 × 10−9, including 27 novel GEI associations, which highlights the effectiveness of fastGWA-GE in GEI signal discovery in large-scale GWAS.
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