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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.

Original publication

DOI

10.1038/s41467-018-03202-2

Type

Journal article

Journal

Nature communications

Publication Date

03/2018

Volume

9

Addresses

Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada.

Keywords

Humans, Air Pollution, Environmental Exposure, Gene Expression, Penetrance, Polymorphism, Genetic, Quantitative Trait Loci, Adult, Aged, Middle Aged, Quebec, France, Gene Flow, Gene-Environment Interaction, Transcriptome