Faculty, Staff and Student Publications

Publication Date

1-1-2022

Journal

Frontiers in Genetics

Abstract

Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium's Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment interactions, yet accessing and harmonizing individual-level genetic and 'omics data is challenging. Here, we demonstrate the coordinated use of summary-level data for gene-lifestyle interaction associations on up to 600,000 individuals, differential methylation data, and gene expression data for the characterization and prioritization of loci for future follow-up analyses. Using this approach, we identify 48 genes for which there are multiple sources of functional support for the identified gene-lifestyle interaction. We also identified five genes for which differential expression was observed by the same lifestyle factor for which a gene-lifestyle interaction was found. For instance, in gene-lifestyle interaction analysis, the T allele of rs6490056 (

Keywords

multi-omics, gene-lifestyle interactions, smoking, alcohol, serum lipids, blood pressure, summary data

DOI

10.3389/fgene.2022.95471

PMID

36544485

PMCID

PMC9760722

PubMedCentral® Posted Date

12-5-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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