- Main
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification
- Kavousi, Maryam;
- Bos, Maxime M;
- Barnes, Hanna J;
- Lino Cardenas, Christian L;
- Wong, Doris;
- Lu, Haojie;
- Hodonsky, Chani J;
- Landsmeer, Lennart PL;
- Turner, Adam W;
- Kho, Minjung;
- Hasbani, Natalie R;
- de Vries, Paul S;
- Bowden, Donald W;
- Chopade, Sandesh;
- Deelen, Joris;
- Benavente, Ernest Diez;
- Guo, Xiuqing;
- Hofer, Edith;
- Hwang, Shih-Jen;
- Lutz, Sharon M;
- Lyytikäinen, Leo-Pekka;
- Slenders, Lotte;
- Smith, Albert V;
- Stanislawski, Maggie A;
- van Setten, Jessica;
- Wong, Quenna;
- Yanek, Lisa R;
- Becker, Diane M;
- Beekman, Marian;
- Budoff, Matthew J;
- Feitosa, Mary F;
- Finan, Chris;
- Hilliard, Austin T;
- Kardia, Sharon LR;
- Kovacic, Jason C;
- Kral, Brian G;
- Langefeld, Carl D;
- Launer, Lenore J;
- Malik, Shaista;
- Hoesein, Firdaus AA Mohamed;
- Mokry, Michal;
- Schmidt, Reinhold;
- Smith, Jennifer A;
- Taylor, Kent D;
- Terry, James G;
- van der Grond, Jeroen;
- van Meurs, Joyce;
- Vliegenthart, Rozemarijn;
- Xu, Jianzhao;
- Young, Kendra A;
- Zilhão, Nuno R;
- Zweiker, Robert;
- Assimes, Themistocles L;
- Becker, Lewis C;
- Bos, Daniel;
- Carr, J Jeffrey;
- Cupples, L Adrienne;
- de Kleijn, Dominique PV;
- de Winther, Menno;
- den Ruijter, Hester M;
- Fornage, Myriam;
- Freedman, Barry I;
- Gudnason, Vilmundur;
- Hingorani, Aroon D;
- Hokanson, John E;
- Ikram, M Arfan;
- Išgum, Ivana;
- Jacobs, David R;
- Kähönen, Mika;
- Lange, Leslie A;
- Lehtimäki, Terho;
- Pasterkamp, Gerard;
- Raitakari, Olli T;
- Schmidt, Helena;
- Slagboom, P Eline;
- Uitterlinden, André G;
- Vernooij, Meike W;
- Bis, Joshua C;
- Franceschini, Nora;
- Psaty, Bruce M;
- Post, Wendy S;
- Rotter, Jerome I;
- Björkegren, Johan LM;
- O’Donnell, Christopher J;
- Bielak, Lawrence F;
- Peyser, Patricia A;
- Malhotra, Rajeev;
- van der Laan, Sander W;
- Miller, Clint L
- et al.
Published Web Location
https://doi.org/10.1038/s41588-023-01518-4Abstract
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.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
Enter the password to open this PDF file:
-
-
-
-
-
-
-
-
-
-
-
-
-
-