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Nat Commun. 2018 Mar 6;9(1):827. doi: 10.1038/s41467-018-03202-2.

Gene-by-environment interactions in urban populations modulate risk phenotypes.

Author information

1
Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada.
2
Sainte-Justine Research Center, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1C5, Canada.
3
Department of Medical and Molecular Genetics, Guy's Hospital, King's College London, London, WC2R 2LS, UK.
4
Statistics Canada, Ottawa, ON, K1A 0T6, Canada.
5
Department of Environmental Health and Occupational Health, University of Montreal, Montreal, QC, H3N 1X9, Canada.
6
Health Canada, Air Health Science Division, Ottawa, ON, K1A 0K9, Canada.
7
NYU Abu Dhabi, Abu Dhabi, UAE.
8
Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada. Philip.Awadalla@oicr.on.ca.
9
Sainte-Justine Research Center, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1C5, Canada. Philip.Awadalla@oicr.on.ca.
10
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A1, Canada. Philip.Awadalla@oicr.on.ca.
11
Ontario Health Study, Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada. Philip.Awadalla@oicr.on.ca.

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.

PMID:
29511166
PMCID:
PMC5840419
DOI:
10.1038/s41467-018-03202-2
[Indexed for MEDLINE]
Free PMC Article

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