Integrative multi-ancestry genetic analysis of gene regulation in coronary arteries prioritizes disease risk loci.
medRxiv
; 2023 Feb 14.
Article
en En
| MEDLINE
| ID: mdl-36824883
Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWAS and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotype information to identify quantitative trait loci (QTL) for gene expression and splicing in coronary arteries obtained from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported in coronary arteries and 19% exhibited cell-type-specific expression. Colocalization analysis with GWAS identified subgroups of eGenes unique to CAD and blood pressure. Fine-mapping highlighted additional eGenes of interest, including TBX20 and IL5 . Splicing (s)QTLs for 1,690 genes were also identified, among which TOR1AIP1 and ULK3 sQTLs demonstrated the importance of evaluating splicing events to accurately identify disease-relevant gene expression. Our work provides the first human coronary artery eQTL resource from a patient sample and exemplifies the necessity of diverse study populations and multi-omic approaches to characterize gene regulation in critical disease processes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Idioma:
En
Revista:
MedRxiv
Año:
2023
Tipo del documento:
Article
Pais de publicación:
Estados Unidos