@article{ac761694637747bf8caac5f4434b04ff,
title = "Large-scale genome-wide association study of coronary artery disease in genetically diverse populations",
abstract = "We report a genome-wide association study (GWAS) of coronary artery disease (CAD) incorporating nearly a quarter of a million cases, in which existing studies are integrated with data from cohorts of white, Black and Hispanic individuals from the Million Veteran Program. We document near equivalent heritability of CAD across multiple ancestral groups, identify 95 novel loci, including nine on the X chromosome, detect eight loci of genome-wide significance in Black and Hispanic individuals, and demonstrate that two common haplotypes at the 9p21 locus are responsible for risk stratification in all populations except those of African origin, in which these haplotypes are virtually absent. Moreover, in the largest GWAS for angiographically derived coronary atherosclerosis performed to date, we find 15 loci of genome-wide significance that robustly overlap with established loci for clinical CAD. Phenome-wide association analyses of novel loci and polygenic risk scores (PRSs) augment signals related to insulin resistance, extend pleiotropic associations of these loci to include smoking and family history, and precisely document the markedly reduced transferability of existing PRSs to Black individuals. Downstream integrative analyses reinforce the critical roles of vascular endothelial, fibroblast, and smooth muscle cells in CAD susceptibility, but also point to a shared biology between atherosclerosis and oncogenesis. This study highlights the value of diverse populations in further characterizing the genetic architecture of CAD.",
author = "{Regeneron Genetics Center} and {CARDIoGRAMPlusC4D Consortium} and {Biobank Japan} and {Million Veteran Program} and Catherine Tcheandjieu and Xiang Zhu and Hilliard, {Austin T.} and Clarke, {Shoa L.} and Valerio Napolioni and Shining Ma and Lee, {Kyung Min} and Huaying Fang and Fei Chen and Yingchang Lu and Tsao, {Noah L.} and Sridharan Raghavan and Satoshi Koyama and Gorman, {Bryan R.} and Marijana Vujkovic and Derek Klarin and Levin, {Michael G.} and Nasa Sinnott-Armstrong and Wojcik, {Genevieve L.} and Plomondon, {Mary E.} and Maddox, {Thomas M.} and Waldo, {Stephen W.} and Bick, {Alexander G.} and Saiju Pyarajan and Jie Huang and Rebecca Song and Ho, {Yuk Lam} and Steven Buyske and Charles Kooperberg and Jeffrey Haessler and Loos, {Ruth J.F.} and Ron Do and Marie Verbanck and Kumardeep Chaudhary and North, {Kari E.} and Avery, {Christy L.} and Mariaelisa Graff and Haiman, {Christopher A.} and {Le Marchand}, Lo{\"i}c and Wilkens, {Lynne R.} and Bis, {Joshua C.} and Hampton Leonard and Botong Shen and Lange, {Leslie A.} and Ayush Giri and Ozan Dikilitas and Kullo, {Iftikhar J.} and Stanaway, {Ian B.} and Jarvik, {Gail P.} and Gordon, {Adam S.} and Scott Hebbring and Bahram Namjou and Kaufman, {Kenneth M.} and Kaoru Ito and Kazuyoshi Ishigaki and Yoichiro Kamatani and Verma, {Shefali S.} and Ritchie, {Marylyn D.} and Kember, {Rachel L.} and Aris Baras and Lotta, {Luca A.} and Sekar Kathiresan and Hauser, {Elizabeth R.} and Miller, {Donald R.} and Lee, {Jennifer S.} and Danish Saleheen and Reaven, {Peter D.} and Kelly Cho and Gaziano, {J. Michael} and Pradeep Natarajan and Huffman, {Jennifer E.} and Voight, {Benjamin F.} and Rader, {Daniel J.} and Chang, {Kyong Mi} and Lynch, {Julie A.} and Damrauer, {Scott M.} and Wilson, {Peter W.F.} and Hua Tang and Sun, {Yan V.} and Tsao, {Philip S.} and O{\textquoteright}Donnell, {Christopher J.} and Assimes, {Themistocles L.}",
note = "Publisher Copyright: {\textcopyright} 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2022",
month = aug,
doi = "10.1038/s41591-022-01891-3",
language = "English",
volume = "28",
pages = "1679--1692",
journal = "Nature medicine",
issn = "1078-8956",
number = "8",
}