School of Medicine Publications and Presentations
Document Type
Article
Publication Date
12-1-2023
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 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 (ARSE and MMP16), with evidence of significant associations in replication analyses for both novel loci. Functional assays of ARSE and MMP16 in human vascular smooth muscle cells (VSMCs) demonstrate that ARSE 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 ARSE with reduced CAC is likely explained by reduced ARSE 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.
Recommended Citation
de Vries, P. S., Conomos, M. P., Singh, K., Nicholson, C. J., Jain, D., Hasbani, N. R., Jiang, W., Lee, S., Lino Cardenas, C. L., Lutz, S. M., Wong, D., Guo, X., Yao, J., Young, E. P., Tcheandjieu, C., Hilliard, A. T., Bis, J. C., Bielak, L. F., Brown, M. R., Musharoff, S., … Malhotra, R. (2023). Whole-genome sequencing uncovers two loci for coronary artery calcification and identifies ARSE as a regulator of vascular calcification. Nature cardiovascular research, 2(12), 1159–1172. https://doi.org/10.1038/s44161-023-00375-y
First Page
1159
Last Page
1172
Publication Title
Nature Cardiovascular Research
DOI
10.1038/s44161-023-00375-y
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
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