Kavousi, Maryam;
Bos, Maxime M;
Barnes, Hanna J;
Cardenas, Christian L Lino;
Wong, Doris;
Lu, Haojie;
Hodonsky, Chani J;
... Miller, Clint L; + view all
(2023)
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification.
Nature Genetics
, 55
(10)
pp. 1651-1664.
10.1038/s41588-023-01518-4.
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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.
| Type: | Article |
|---|---|
| Title: | Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41588-023-01518-4 |
| Publisher version: | https://doi.org/10.1038/s41588-023-01518-4 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, BEAM COMPUTED-TOMOGRAPHY, LD SCORE REGRESSION, MENDELIAN RANDOMIZATION, RISK CLASSIFICATION, BLOOD-PRESSURE, CALCIUM SCORE, ASSOCIATION, DISEASE, LOCI, ATHEROSCLEROSIS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10183027 |
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