Whole-genome sequencing uncovers two loci for coronary artery calcification and identifies ARSE as a regulator of vascular calcification.
| Authors | |
| Abstract | Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study (GWAS) of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC ( and ), with evidence of significant associations in replication analyses for both novel loci. Functional assays of and in human vascular smooth muscle cells (VSMCs) demonstrate that is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying or osteogenic phenotype. Furthermore, we show that the association of variants near with reduced CAC is likely explained by reduced expression with the G allele of enhancer variant rs5982944. Our study highlights ARSE as an important contributor to atherosclerotic vascular calcification, and a potential drug target for vascular calcific disease. |
| Year of Publication | 2023
|
| Journal | Nature cardiovascular research
|
| Volume | 2
|
| Issue | 12
|
| Pages | 1159-1172
|
| Date Published | 12/2023
|
| ISSN | 2731-0590
|
| DOI | 10.1038/s44161-023-00375-y
|
| PubMed ID | 38817323
|
| Links |