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

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

Panos Deloukas^a✉, Stavroula Kanoni^a, Christina Willenborg^b, Martin Farrall^{c d}, Themistocles L. Assimes^e, John R. Thompson^f, Erik Ingelsson^g, Danish Saleheen^{h i j}, Jeanette Erdmann^b, Benjamin Alan Goldstein^e, Kathleen E. Stirrups^a,

Nature Genetics Nature Portfolio2012-12-02 1,664 citations37 references

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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 (r2 < 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.

TL;DRAn association analysis in CAD cases and controls identifies 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants strongly associated with CAD at a 5% false discovery rate (FDR). (Semantic Scholar)

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Discussion

^aWellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
^bInstitut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany
^cRadcliffe Department of Medicine, Cardiovascular Medicine, University of Oxford, Oxford, UK
^dWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
^eDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA
^fDepartment of Health Sciences, University of Leicester, Leicester, UK
^gDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
^hCenter for Non-Communicable Diseases, Karachi, Pakistan
ⁱDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
^jDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK
^kInstitut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany
^lUppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
^mDivision of Cardiovascular and Neuronal Remodelling, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
ⁿCenter for Genome Science, Korea National Institute of Health, Korea Center for Disease Control and Prevention, Yeonje-ri, Chungwon-gun, Korea
^oDepartment of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA
^pDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
^qDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK
^rEstonian Genome Center, University of Tartu, Tartu, Estonia
^sInstitute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
^tCenter for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
^uDepartment of Medicine, Atherosclerosis Research Unit, Karolinska Institutet, Stockholm, Sweden
^vDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK
^wDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
^xClinical Trial Service Unit, University of Oxford, Oxford, UK
^yEpidemiological Studies Unit, University of Oxford, Oxford, UK
^zLudwigshafen Risk and Cardiovascular Health (LURIC) Study, Freiburg, Germany
^aaMannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany
^abDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden
^acDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland
^adDepartment of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland
✉Corresponding author