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Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification.
Tuesday,2023-10-10 12:25 America/Los_Angeles — ecterry
| Title | Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Kavousi, M, Bos, MM, Barnes, HJ, Cardenas, CLLino, Wong, D, Lu, H, Hodonsky, CJ, Landsmeer, LPL, Turner, AW, Kho, M, Hasbani, NR, de Vries, PS, Bowden, DW, Chopade, S, Deelen, J, Benavente, EDiez, Guo, X, Hofer, E, Hwang, S-J, Lutz, SM, Lyytikäinen, L-P, Slenders, L, Smith, AV, Stanislawski, MA, van Setten, J, Wong, Q, Yanek, LR, Becker, DM, Beekman, M, Budoff, MJ, Feitosa, MF, Finan, C, Hilliard, AT, Kardia, SLR, Kovacic, JC, Kral, BG, Langefeld, CD, Launer, LJ, Malik, S, Hoesein, FAAMohame, Mokry, M, Schmidt, R, Smith, JA, Taylor, KD, Terry, JG, van der Grond, J, van Meurs, J, Vliegenthart, R, Xu, J, Young, KA, Zilhão, NR, Zweiker, R, Assimes, TL, Becker, LC, Bos, D, J Carr, J, Cupples, AL, de Kleijn, DPV, de Winther, M, Ruijter, HM den, Fornage, M, Freedman, BI, Gudnason, V, Hingorani, AD, Hokanson, JE, Ikram, AM, Išgum, I, Jacobs, DR, Kähönen, M, Lange, LA, Lehtimäki, T, Pasterkamp, G, Raitakari, OT, Schmidt, H, P Slagboom, E, Uitterlinden, AG, Vernooij, MW, Bis, JC, Franceschini, N, Psaty, BM, Post, WS, Rotter, JI, Björkegren, JLM, O'Donnell, CJ, Bielak, LF, Peyser, PA, Malhotra, R, van der Laan, SW, Miller, CL |
| Journal | Nat Genet |
| Volume | 55 |
| Issue | 10 |
| Pagination | 1651-1664 |
| Date Published | 2023 Oct |
| ISSN | 1546-1718 |
| Abstract | <p>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.</p> |
| DOI | 10.1038/s41588-023-01518-4 |
| Alternate Journal | Nat Genet |
| PubMed ID | 37770635 |
| PubMed Central ID | 3033741 |
| Grant List | K01 HL164687 / HL / NHLBI NIH HHS / United States R01 HL163972 / HL / NHLBI NIH HHS / United States R01 HL163972 / HL / NHLBI NIH HHS / United States |
ePub date:
09/23