Faculty, Staff and Student Publications
Publication Date
10-1-2023
Journal
Nature Genetics
Abstract
Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci are related to bone mineralization, phosphate catabolism and hormone metabolic pathways. Several new loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC and extend our understanding of the biological and potential druggable pathways underlying CAC.
Keywords
Humans, Atherosclerosis, Black People, Coronary Artery Disease, Genome-Wide Association Study, Risk Factors, European People
DOI
10.1038/s41588-023-01518-4
PMID
37770635
PMCID
PMC10601987
PubMedCentral® Posted Date
10-26-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Genetics Commons, Genomics Commons, Medical Genetics Commons, Public Health Commons