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