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

• DOI: 10.1101/2023.02.09.23285622
• Publication Date: 2023-02-14T18:56:22Z
• 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: Coronary arteries

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 these during atherosclerosis remain unclear. We incorporated local ancestry haplotype information to identify quantitative trait (QTL) gene expression splicing arteries obtained from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported 19% exhibited cell-type-specific expression. Colocalization analysis with subgroups eGenes unique CAD blood pressure. Fine-mapping highlighted additional interest, including