Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

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

doi:10.1038/ng.3874

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Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Journal article

Peer reviewed

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Joanna M M Howson, Wei Zhao, Daniel R Barnes, Weang-Kee Ho, Robin Young, Dirk S Paul, Lindsay L Waite, Daniel F Freitag, Eric B Fauman, Elias L Salfati, …

Nature genetics, Vol.49(7), pp.1113-1119

01/07/2017

DOI: https://doi.org/10.1038/ng.3874

PMCID: PMC5555387

PMID: 28530674

Abstract

Arteries - pathology

Atherosclerosis - genetics

Cell Adhesion - genetics

Chemotaxis, Leukocyte - genetics

Coronary Artery Disease - genetics

Coronary Artery Disease - pathology

Coronary Artery Disease - physiopathology

Energy Metabolism - genetics

Female

Genetic Predisposition to Disease

Genome-Wide Association Study

Genotype

Histone Code

Humans

Male

Muscle, Smooth, Vascular - pathology

Polymorphism, Single Nucleotide

Quantitative Trait Loci

Risk Factors

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 × 10 , 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.

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Title: Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms
Creators - without role: Joanna M M Howson - University of Cambridge
Wei Zhao - University of Pennsylvania
Daniel R Barnes - University of Pennsylvania
Weang-Kee Ho - University of Cambridge
Robin Young - University of Cambridge
Dirk S Paul - University of Glasgow
Lindsay L Waite - University of Cambridge
Daniel F Freitag - HudsonAlpha Institute for Biotechnology
Eric B Fauman - University of Cambridge
Elias L Salfati - Pfizer
Benjamin B Sun - Cardiovascular Institute of the South
John D Eicher - University of Cambridge
Andrew D Johnson - National Heart Lung and Blood Institute
Wayne H H Sheu - Framingham Heart Study
Sune F Nielsen - Copenhagen University Hospital
Wei-Yu Lin - Gentofte Hospital
Praveen Surendran - University of Cambridge
Anders Malarstig - University of Cambridge
Jemma B Wilk - Pfizer
Anne Tybjærg-Hansen - Pfizer
Katrine L Rasmussen - Copenhagen University Hospital
Pia R Kamstrup - Gentofte Hospital
Panos Deloukas - Gentofte Hospital
Jeanette Erdmann - Queen Mary University of London
Sekar Kathiresan - University of Lübeck
Nilesh J Samani - Massachusetts General Hospital
Heribert Schunkert - University of Leicester
Hugh Watkins - German Centre for Cardiovascular Research
Ron Do - Icahn School of Medicine at Mount Sinai
Daniel J Rader - University of Pennsylvania
Julie A Johnson - University of Florida
Stanley L Hazen - Cleveland Clinic Lerner College of Medicine
Arshed A Quyyumi - Emory University
John A Spertus - University of Missouri–Kansas City
Carl J Pepine - University of Florida
Nora Franceschini - University of North Carolina at Chapel Hill
Anne Justice - University of North Carolina at Chapel Hill
Alex P Reiner - University of Washington
Steven Buyske - Rutgers, The State University of New Jersey
Lucia A Hindorff - National Human Genome Research Institute
Cara L Carty - Fred Hutch Cancer Center
Kari E North - University of North Carolina at Chapel Hill
Charles Kooperberg - Fred Hutch Cancer Center
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Kristin Young - University of North Carolina at Chapel Hill
Mariaelisa Graff - University of North Carolina at Chapel Hill
Ulrike Peters - Fred Hutch Cancer Center
Devin Absher - HudsonAlpha Institute for Biotechnology
Chao A Hsiung - National Health Research Institutes
Wen-Jane Lee - Taichung Veterans General Hospital
Kent D Taylor - Ronald Reagan UCLA Medical Center
Ying-Hsiang Chen - National Health Research Institutes
I-Te Lee - Chung Shan Medical University
Xiuqing Guo - The Lundquist Institute
Ren-Hua Chung - National Health Research Institutes
Yi-Jen Hung - National Defense Medical Center
Jerome I Rotter - Harbor–UCLA Medical Center
Jyh-Ming J Juang - National Taiwan University Hospital
Thomas Quertermous - Cardiovascular Institute of the South
Tzung-Dau Wang - National Taiwan University Hospital
Asif Rasheed - Center for Non-Communicable Diseases
Philippe Frossard - Center for Non-Communicable Diseases
Dewan S Alam - York University
Abdulla Al Shafi Majumder - National Institute of Cardiovascular Diseases, Sher-e-Bangla Nagar, Bangladesh
Emanuele Di Angelantonio - University of Cambridge
Rajiv Chowdhury - University of Cambridge
Yii-Der Ida Chen - Gentofte Hospital
Børge G Nordestgaard - Cardiovascular Institute of the South
Themistocles L Assimes - Wellcome Sanger Institute
John Danesh - National Institute for Health Research
Adam S Butterworth - University of Cambridge
Danish Saleheen - Centre for Non-Communicable Disease, Karachi, Pakistan
EPIC-CVD
Publication Details: Nature genetics, Vol.49(7), pp.1113-1119
Grant note: S10 OD020069 / NIH HHS R21 HL123677 / NHLBI NIH HHS UL1 TR001881 / NCATS NIH HHS MR/L003120/1 / Medical Research Council G0800270 / Medical Research Council CH/12/2/29428 / British Heart Foundation R56 DK104806 / NIDDK NIH HHS P30 ES010126 / NIEHS NIH HHS 1508647 / Medical Research Council K23 DK088942 / NIDDK NIH HHS RG/08/014/24067 / British Heart Foundation SP/09/002/27676 / British Heart Foundation K99 HL130580 / NHLBI NIH HHS RG/14/5/30893 / British Heart Foundation UL1 TR000124 / NCATS NIH HHS T32 HL098049 / NHLBI NIH HHS SP/02/002/14543 / British Heart Foundation P30 DK063491 / NIDDK NIH HHS 268834 / European Research Council
Identifiers: 9937999708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article