An international consortium of scientists reports the discovery of five new genes that affect the risk of developing coronary artery disease (CAD) and heart attacks in a study to be published in the open-access journal PLoS Genetics on September 22nd.
Coronary artery disease is the most common cause of premature death and disability in the world and has a strong but incompletely characterised genetic contribution. The identification of the roles of various genes in the onset of heart disease could help in the development of new treatments and improve prediction of CAD. The study also demonstrated that some associations between genes and CAD, suggested by other, smaller studies, are spurious, according to Dr Adam Butterworth, who co-ordinated the analysis.
The consortium examined 49,094 genetic variants in ~2,100 genes of cardiovascular relevance in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent, and 4,394 cases and 4,259 controls of South Asian origin) and replicated their principal findings in an additional 17,121 CAD cases and 40,473 controls.
"This is one of the first genetic studies of CAD to include a significant proportion of subjects of South Asian origin, an ethnic group that has a higher risk of CAD," says Professor John Danesh, co-principal investigator. "Our study shows that many of the genes that affect risk of CAD do so similarly in European Caucasians as in South Asians."
The study adds to the growing list of genes, now over 30, that affect risk of CAD and heart attacks. Co-principal investigator Professor Nilesh Samani (British Heart Foundation Professor of Cardiology University of Leicester, UK) says: "The findings provide new insights into and understanding of the causal biological pathways that cause heart disease, and particularly highlight the role of lipids and inflammation."
"Although the effects of the new genetic variants that we have identified are individually small, in the order of 5-10% per copy, new treatments that are developed on the basis of the findings could have a much broader effect, as we have learnt, for example, with statins," adds Professor Hugh Watkins (British Heart Foundation Professor of Cardiovascular Medicine, University of Oxford), also a co-principal investigator.
FINANCIAL DISCLOSURE: BHF-FHS: Recruitment of CAD cases for the BHF-FHS study was supported by the British Heart Foundation (BHF) and the UK Medical Research Council. Controls were provided by the Wellcome Trust Case Control Consortium. Genotyping of the IBC 50K array for the BHF-FHS study was funded by the BHF. NJS and SGB hold personal chairs supported by the BHF. The work described in this paper forms part of the portfolio of translational research supported by the Leicester NIHR Biomedical Research Unit in Cardiovascular Disease. BLOODOMICS: The Bloodomics partners from AMC (The Netherlands), LURIC (Germany), the University of Cambridge (UK), and the Wellcome Trust Sanger Institute (UK) received funding through the 6th Framework funded Integrated Project Bloodomics (grant LSHM-CT-2004-503485). The University of Cambridge group in the Department of Haematology also received programme grant funding from the British Heart Foundation (RG/09/12/28096) and the National Institute for Health Research (RP-PG-0310-1002). BLOODOMICS-Dutch: This study was supported by research grants from The Netherlands Heart Foundation (grants 2001D019, 2003T302 and 2007B202), the Leducq Foundation (grant 05-CVD), the Center for Translational Molecular Medicine (CTMM COHFAR), and the Interuniversity Cardiology Institute of The Netherlands (project 27). BLOODOMICS-German: LURIC has received funding through the 6th Framework Program (integrated project Bloodomics, grant LSHM-CT-2004-503485) and 7th Framework Program (integrated project Atheroremo, Grant Agreement number 201668) of the European Union. CARe Consortium: CARe was performed with the support of the National Heart, Lung, and Blood Institute and acknowledges the contributions of the research institutions, study investigators, and field staff in creating this resource for biomedical research. Full details of the studies in the CARe Consortium can be found in Text S1. LOLIPOP: Genotyping of the IBC 50K array for the LOLIPOP Study was funded by the British Heart Foundation. Paul Elliott is a National Institute for Health Research Senior Investigator. MONICA-KORA: The MONICA/KORA Augsburg studies were financed by the Helmholtz Zentrum Mu¨ nchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF). Part of this work was financed by the German National Genome Research Network (NGFNPlus, project number 01GS0834) and through additional funds from the University of Ulm. Furthermore, the research was supported within the Munich Center of Health Sciences (MC Health) as part of LMU innovative. PennCATH: Muredach P Reilly and Daniel J Rader have been supported by the Penn Cardiovascular Institute and GlaxoSmithKline. PROCARDIS: The PROCARDIS study has been supported by the British Heart Foundation, the European Community Sixth Framework Program (LSHM-CT-2007-037273), AstraZeneca, the Wellcome Trust, the United Kingdom Medical Research Council, the Swedish Heart-Lung Foundation, the Swedish Medical Research Council, the Knut and Alice Wallenberg Foundation, the Torsten and Ragnar So¨derberg Foundation, the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council (560283). PROMIS: Epidemiological field work in PROMIS was supported by unrestricted grants to investigators at the University of Cambridge and in Pakistan. Genotyping for this study was funded by the Wellcome Trust and the EU Framework 6-funded Bloodomics Integrated Project (LSHM-CT-2004-503485). The British Heart Foundation has supported some biochemical assays. The Yousef Jameel Foundation supported D Saleheen. The cardiovascular disease epidemiology group of J Danesh is underpinned by programme grants from the British Heart Foundation and the UK Medical Research Council. EPIC-NL: The EPIC-NL study was funded by ''Europe against Cancer'' Programme of the European Commission (SANCO); the Dutch Ministry of Health; the Dutch Cancer Society; ZonMW the Netherlands Organisation for Health Research and Development; World Cancer Research Fund (WCRF). We thank the institute PHARMO for follow-up data on diabetes. Genotyping was funded by IOP Genomics grant IGE 05012 from NL Agency. UCP: The project was funded by Veni grant Organization for Scientific Research (NWO), Grant no. 2001.064 Netherlands Heart Foundation (NHS), and TI Pharma Grant T6-101 Mondriaan. Cardiogenics: Cardiogenics was funded through the 6th Framework Programme (integrated project Cardiogenics, grant LSHM-CT-2006-037593) of the European Union. None of the sponsors had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.
COMPETING INTERESTS: Muredach P Reilly and Daniel J Rader have a research grant from GlaxoSmithKline. The division of Pharmacoepidemiology and Clinical Pharmacology employing Bas Peters, Olaf Klungel, Anthonius de Boer, and Anke-Hilse Maitland-van der Zee has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private-public funded Top Institute Pharma (www.tipharma.nl, includes co-funding from universities, government, and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health. Arthur AM Wilde is a consultant for Transgenomics (Familion test) and Sorin. No other disclosures were reported.
CITATION: The IBC 50K CAD Consortium (2011) Large-Scale Gene-Centric Analysis Identifies Novel Variants for Coronary Artery Disease. PLoS Genet 7(9): e1002260. doi:10.1371/journal.pgen.1002260
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CONTACT: Professor Nilesh J Samani
University of Leicester
+44 (0)116 2563021
Professor Hugh Watkins
University of Oxford, +44 (0)1865 220257
Professor John Danesh
University of Cambridge
+44  1223 741302
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