Multi-ancestry genetic analysis of gene regulation in coronary artery prioritizes disease risk loci
Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in 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. Overall design: We integrated bulk RNA-sequencing and low-pass whole-genome seqeuncing to map allele-specific expression, eQTL and sQTL in coronary artery tissues from patients across a range of atherosclerosis disease stages. We leverage these molecular traits to perform colocalization based fine-mapping with CAD and related risk factors.