Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification

Kavousi, Maryam and Bos, Maxime M. and Barnes, Hanna J. and Lino Cardenas, Christian L. and Wong, Doris and Lu, Haojie and Hodonsky, Chani J. and Landsmeer, Lennart P. L. and Turner, Adam W. and Kho, Minjung and Hasbani, Natalie R. and de Vries, Paul S. and Bowden, Donald W. and Chopade, Sandesh and Deelen, Joris and Benavente, Ernest Diez and Guo, Xiuqing and Hofer, Edith and Hwang, Shih-Jen and Lutz, Sharon M. and Lyytikäinen, Leo-Pekka and Slenders, Lotte and Smith, Albert V. and Stanislawski, Maggie A. and van Setten, Jessica and Wong, Quenna and Yanek, Lisa R. and Becker, Diane M. and Beekman, Marian and Budoff, Matthew J. and Feitosa, Mary F. and Finan, Chris and Hilliard, Austin T. and Kardia, Sharon L. R. and Kovacic, Jason C. and Kral, Brian G. and Langefeld, Carl D. and Launer, Lenore J. and Malik, Shaista and Hoesein, Firdaus A. A. Mohamed and Mokry, Michal and Schmidt, Reinhold and Smith, Jennifer A. and Taylor, Kent D. and Terry, James G. and van der Grond, Jeroen and van Meurs, Joyce and Vliegenthart, Rozemarijn and Xu, Jianzhao and Young, Kendra A. and Zilhão, Nuno R. and Zweiker, Robert and Assimes, Themistocles L. and Becker, Lewis C. and Bos, Daniel and Carr, J. Jeffrey and Cupples, L. Adrienne and de Kleijn, Dominique P. v. and de Winther, Menno and den Ruijter, Hester M. and Fornage, Myriam and Freedman, Barry I. and Gudnason, Vilmundur and Hingorani, Aroon D. and Hokanson, John E. and Ikram, M. Arfan and Išgum, Ivana and Jacobs, David R. and Kähönen, Mika and Lange, Leslie A. and Lehtimäki, Terho and Pasterkamp, Gerard and Raitakari, Olli T. and Schmidt, Helena and Slagboom, P. Eline and Uitterlinden, André G. and Vernooij, Meike W. and Bis, Joshua C. and Franceschini, Nora and Psaty, Bruce M. and Post, Wendy S. and Rotter, Jerome I. and Björkegren, Johan L. M. and O’Donnell, Christopher J. and Bielak, Lawrence F. and Peyser, Patricia A. and Malhotra, Rajeev and van der Laan, Sander W. and Miller, Clint L. (2023) Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification. Nature Genetics, 55 (10). pp.1651-1664. ISSN 1061-4036

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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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 01 May 2024 04:47
Last Modified: 01 May 2024 04:47

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