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

Research output: Contribution to journalArticle

Marie-Julie Fave, Fabien Lamaze, David Soave, Alan Hodgkinson, Heloise Gauvin, Vanessa Bruat, Jean-Christophe Grenier, Elias Gbeha, Kimberly Skead, Audrey Smargiassi, Markey Johnson, Youssef Idaghdour, Philip Awadalla

Original languageEnglish
Article number827
JournalNature Communications
Early online date6 Mar 2018
StateE-pub ahead of print - 6 Mar 2018


King's Authors


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.

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