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

Marie-Julie Favé, Fabien C. Lamaze, David Soave, Alan Hodgkinson, Héloïse Gauvin, Vanessa Bruat, Jean-Christophe Grenier, Elias Gbeha, Kimberly Skead, Audrey Smargiassi, Markey Johnson, Youssef Idaghdour and Philip Awadalla ()
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Marie-Julie Favé: Ontario Institute for Cancer Research
Fabien C. Lamaze: Ontario Institute for Cancer Research
David Soave: Ontario Institute for Cancer Research
Alan Hodgkinson: University of Montreal
Héloïse Gauvin: University of Montreal
Vanessa Bruat: Ontario Institute for Cancer Research
Jean-Christophe Grenier: Ontario Institute for Cancer Research
Elias Gbeha: Ontario Institute for Cancer Research
Kimberly Skead: Ontario Institute for Cancer Research
Audrey Smargiassi: University of Montreal
Markey Johnson: Air Health Science Division
Youssef Idaghdour: NYU Abu Dhabi
Philip Awadalla: Ontario Institute for Cancer Research

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03202-2

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