Fifteen New Risk Loci for Coronary Artery Disease Highlight Arterial-Wall-Specific Mechanisms

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Howson, Joanna M. M.; Zhao, Wei; Barnes, Daniel R.; Ho, Weang-Kee; Young, Robin D.; Paul, Dirk S.; Waite, Lindsay L.; Freitag, Daniel F.; Fauman, Eric B.; & Salfati, Elias L., et al. (2017). Fifteen New Risk Loci for Coronary Artery Disease Highlight Arterial-Wall-Specific Mechanisms. Nature Genetics, 49(7), 1113-1121. PMCID: PMC5555387

Abstract

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 x 10-8, in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.

URL

http://dx.doi.org/10.1038/ng.3874

Reference Type

Journal Article

Year Published

2017

Journal Title

Nature Genetics

Author(s)

Howson, Joanna M. M.
Zhao, Wei
Barnes, Daniel R.
Ho, Weang-Kee
Young, Robin D.
Paul, Dirk S.
Waite, Lindsay L.
Freitag, Daniel F.
Fauman, Eric B.
Salfati, Elias L.
Sun, Benjamin B.
Eicher, John D.
Johnson, Andrew D.
Sheu, Wayne Huey-Herng
Nielsen, Sune F.
Lin, Wei-Yu
Surendran, Praveen
Malarstig, Anders
Wilk, Jemma B.
Tybjaerg-Hansen, Anne
Rasmussen, Katrine L.
Kamstrup, Pia R.
Deloukas, Panos
Erdmann, Jeanette
Kathiresan, Sekar
Samani, Nilesh J.
Schunkert, Heribert
Watkins, Hugh
CARDIoGRAMplusC4D,
Do, Ron
Rader, Daniel J.
Johnson, Julie A.
Hazen, Stanley L.
Quyyumi, Arshed A.
Spertus, John A.
Pepine, Carl J.
Franceschini, Nora
Justice, Anne E.
Reiner, Alexander P.
Buyske, Steven G.
Hindorff, Lucia A.
Carty, Cara L.
North, Kari E.
Kooperberg, Charles L.
Boerwinkle, Eric A.
Young, Kristin L.
Graff, Mariaelisa
Peters, Ulrike
Absher, Devin M.
Hsiung, Chao A.
Lee, Wen-Jane
Taylor, Kent D.
Chen, Ying-Hsiang
Lee, I-Te
Guo, Xiuqing
Chung, Ren-Hua
Hung, Yi-Jen
Rotter, Jerome I.
Juang, Jyh-Ming J.
Quertermous, Thomas
Wang, Tzung-Dau
Rasheed, Asif
Frossard, Philippe
Alam, Dewan S.
Majumder, Abdulla Al Shafi
Di Angelantonio, Emanuele
Chowdhury, Rajiv
EPIC-CVD Consortium,
Chen, Yii-Der Ida
Nordestgaard, Borge G.
Assimes, Themistocles L.
Danesh, John
Butterworth, Adam S.
Saleheen, Danish

PMCID

PMC5555387

ORCiD

Graff - 0000-0001-6380-1735