Abstract
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.
Highlights
Uncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine
Canada’s precision medicine initiative, the Canadian Partnership for Tomorrow Project (CPTP: http://www. partnershipfortomorrow.ca) is a cohort comprising over 315,000 Canadians, and captures over 700 variables, ranging from longitudinal health information to environmental exposures, to determine genetic and environmental factors contributing to chronic disease
The majority of the Quebec population is of FC descent; a group of individuals descending from French settlers that colonized the Saint-Lawrence Valley from 1608 to the British conquest of 175924
Summary
Uncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine. We find GGT levels to be associated with the differentially expressed genes across SO2 exposure environments, in particular those genes enriched in blood coagulation and platelet regulation (Supplementary Fig. 12), Collectively, these results reveal associations between environmental pollutants, endophenotypic traits, as well as transcript levels, and that the type and direction of associations are consistent with detrimental effects of air pollution, or a correlated variable, on health status.
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