Large-scale association analysis identifies new risk loci for coronary artery disease

Abstract

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

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Affiliated Institutions

• Harokopio University of Athens GR
• University of Dundee GB
• Harvard University US
• Korea Center for Disease Control and Prevention KR
• Universität Ulm DE
• Tampere University Hospital FI
• University Hospital Heidelberg DE
• Umeå University SE
• Ninewells Hospital GB
• Sorbonne Université FR
• King's College London GB
• Reykjavík University IS
• Fondation pour l’innovation en Cadiométabolisme et Nutrition FR
• Medical Research Council GB
• Helmholtz Zentrum München DE
• Deutsches Herzzentrum München DE
• University of Pennsylvania US
• Broad Institute US
• Michigan Medicine US
• Technical University of Munich DE
• Ludwig-Maximilians-Universität München DE
• Karolinska Institutet SE
• Addenbrooke's Hospital GB
• Churchill Hospital GB
• Massachusetts General Hospital US
• Center for Non-Communicable Diseases PK
• deCODE Genetics (Iceland) IS
• Institute for Integrative and Experimental Genomics DE
• University of Leicester GB
• Christian-Albrechts-Universität zu Kiel DE
• Centre for Human Genetics GB
• Institute for Molecular Medicine Finland FI
• Kuopio University Hospital FI
• Finnish Institute for Health and Welfare FI
• Imperial College London GB
• Uppsala University SE
• University of Helsinki FI
• Fimlab (Finland) FI
• Commissariat à l'Énergie Atomique et aux Énergies Alternatives FR
• Pfizer (United States) US
• Onassis Cardiac Surgery Center GR
• University of Cambridge GB
• Sanquin NL
• Hammersmith Hospital GB
• University of Oxford GB
• Lund University SE
• Glenfield Hospital GB
• Tampere University FI
• Zimmer Biomet (Germany) DE
• University of Iceland IS
• Karolinska University Hospital SE
• University of Mannheim DE
• Center for Human Genetics US
• Inserm FR
• University Medical Center of the Johannes Gutenberg University Mainz DE
• Stanford University US
• University of Eastern Finland FI
• Skåne University Hospital SE
• Oxford Centre for Diabetes, Endocrinology and Metabolism GB
• Université Lille Nord de France FR
• HudsonAlpha Institute for Biotechnology US
• Institut Pasteur de Lille FR
• University of Lübeck DE
• University of Michigan US
• MRC Epidemiology Unit GB
• Johannes Gutenberg University Mainz DE
• Wellcome Sanger Institute GB
• University of Leeds GB
• University of Tartu EE
• University of Ottawa CA
• Heidelberg University DE
• Medizinische Hochschule Hannover DE
• Korea National Institute of Health KR
• National University Hospital of Iceland IS

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