The combined impact of genomics and environmental air pollution to the transcriptome in human populations of Quebec
Marie-Julie Favé, Alan Hodgkinson, Fabien C. Lamaze, Héloïse Gauvin, Vanessa Bruat, Jean-Christophe Grenier, Elias Gbeha, Audrey Smargiassi, Markey Johnson, Youssef Idhagdour, and Philip Awadalla
ONTARIO INSTITUTE FOR CANCER RESEARCH AND UNIVERSITÉ DE MONTRÉAL

Uncovering the interactions between genomes and the environment is a main challenge of modern genomics and is key for understanding the making of phenotypes and their evolution. Gene-by-environment interactions are thought to be pervasive and may be responsible for a large fraction of the unexplained variance in heritability, phenotypic variance, as well as in humans, disease risk. To systematically survey genetic, environmental, and interaction effects on gene expression, we combined genome-wide transcriptome RNA-Seq profiling with whole genome genotyping on 1,000 deeply characterized humans selected from the Quebec-based CARTaGENE Biobank. We document a substantial geographic variation in whole blood gene expression profiles in this founder population that follows a south-north cline in the province of Quebec. We were able to attribute gene expression variation to the impact of the regional environment overpowering that of regional ancestry. Using fine-scale environmental data, we discovered that local and daily emissions of air pollution is one of the main factors associated with variation in gene expression in the blood, which in turn affect cardio-metabolic and respiratory traits. Genes involved in oxygen transport and inflammation are enriched among the differentially expressed genes between environments, suggesting an impact of highly urbanized environments on gene expression profiles. We also report several instances of genome-wide significant transcriptional gene-environment interactions (environmental eQTLs) that may have a phenotypic impact for individuals carrying specific genotypes in a given environment. More broadly, our work shows how environmental exposures modulate gene expression directly and indirectly, and can drastically affect phenotypes, including humans.