Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada.
Sainte-Justine Research Center, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1C5, Canada.
Nat Commun. 2018 Mar 6;9(1):827. doi: 10.1038/s41467-018-03202-2.
Uncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine. While theoretical models are well defined, little is known of the G × E interactions in humans. We used an integrative approach to comprehensively assess the interactions between 1.6 million data points, encompassing a range of environmental exposures, health, and gene expression levels, coupled with whole-genome genetic variation. From ∼1000 individuals of a founder population in Quebec, we reveal a substantial impact of the environment on the transcriptome and clinical endophenotypes, overpowering that of genetic ancestry. Air pollution impacts gene expression and pathways affecting cardio-metabolic and respiratory traits, when controlling for genetic ancestry. Finally, we capture four expression quantitative trait loci that interact with the environment (air pollution). Our findings demonstrate how the local environment directly affects disease risk phenotypes and that genetic variation, including less common variants, can modulate individual's response to environmental challenges.
揭示基因组与环境之间的相互作用是现代基因组学和预防医学的主要挑战。虽然理论模型已经得到很好的定义，但人类对 G×E 相互作用知之甚少。我们采用综合方法，全面评估了 160 万个数据点之间的相互作用，这些数据点涵盖了一系列环境暴露、健康和基因表达水平，并结合了全基因组遗传变异。从魁北克一个创始人群体中的约 1000 个人中，我们发现环境对转录组和临床表型有实质性影响，这种影响超过了遗传祖先的影响。在控制遗传祖先的情况下，空气污染会影响影响心血管代谢和呼吸特征的基因表达和途径。最后，我们捕获了四个与环境（空气污染）相互作用的表达数量性状基因座。我们的研究结果表明，当地环境如何直接影响疾病风险表型，以及遗传变异（包括罕见变异）如何调节个体对环境挑战的反应。
