Multi-ancestry genetic analysis of gene regulation in coronary arteries prioritizes disease risk loci

• DOI: 10.1016/j.xgen.2023.100465
• Publication Date: 2023-12-15T16:20:00Z
• Authors: Chani J. Hodonsky; Adam W. Turner; Mohammad Daud Khan; Nelson B. Barrientos; Ruben Methorst; Lijiang Ma; Nicolas G. Lopez; Jose Verdezoto Mo...; Gaëlle Auguste; Emily Farber; Wei Feng Ma; Doris Wong; Suna Onengut-Gumuscu; Maryam Kavousi; Patricia A. Peyser; Sander W. van der...; Nicholas J. Leeper; Jason C. Kovacic; Johan L.M. Björke...; Clint L. Miller
• Keywords: Genome-wide Association Study; Genetic Association

Genome-wide association studies (GWASs) have identified hundreds of risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWASs, and the causal gene-regulatory mechanisms these during atherosclerosis remain unclear. We incorporated local ancestry haplotypes to identify quantitative trait expression (eQTLs) splicing (sQTLs) arteries from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported artery; 19% exhibited cell-type-specific expression. Colocalization revealed subgroups eGenes unique CAD blood pressure GWAS. Fine-mapping highlighted additional eGenes, including TBX20 IL5. also sQTLs 1,690 genes, among which TOR1AIP1 ULK3 demonstrated importance evaluating accurately disease-relevant isoform Our work provides a patient-derived eQTL resource exemplifies need study multifaceted approaches characterize gene regulation processes.