期刊
NATURE GENETICS
卷 49, 期 9, 页码 1385-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3913
关键词
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资金
- British Heart Foundation (BHF) [RG/14/5/30893, FS/14/66/31293]
- UK National Institute for Health Research (NIHR)
- NIHR
- BHF
- Transatlantic Networks of Excellence Award from the Leducq Foundation [12CVD02]
- EU-FP7 [HEALTH-F2-2013-601456, 201668, 305739, HEALTH-F2-2012-279233]
- EU-FP6 [LSHM-CT-2007-037273]
- AstraZeneca
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Swedish Heart-Lung Foundation
- Torsten and Ragnar Soderberg Foundation
- Karolinska Institutet
- Foundation Strategic Research
- Stockholm County Council [560283]
- Wellcome Trust [090532/Z/09/Z, 084723/Z/08/Z, 098051]
- Deutsche Forschungsgemeinschaft Centre of Research Excellence [Sonderforschungsbereich CRC 1123 (B02)]
- FP7 [HEALTH-F2-2013-601456]
- Wellcome Trust
- TriPartite Immunometabolism Consortium-Novo Nordisk Foundation [NNF15CC0018486]
- Medical Research Council (MRC)
- Merck and Co
- Roche Vitamins, Ltd.
- BHF [FS/14/55/30806, SP/04/002, PG/16/49/32176, FS/12/80/29821, SP/09/002]
- Andrea and Charles Bronfman Philanthropies
- European Commission [CoG-2015_681742_NASCENT]
- Swedish Research Council (Distinguished Young Researchers Award)
- Heart-Lung Foundation
- Novo Nordisk Foundation
- Canadian Institutes of Health Research
- Canada Foundation for Innovation
- Heart AMP
- Stroke Foundation of Canada
- European Regional Development Fund (ERDF)
- Wissenschaftsoffensive TMO
- German Ministry for Education and Research [01ZX1313A-K]
- NIHR-BRC Imperial College Healthcare NHS Trust
- MRC [G0601966, G0700931, G0800270]
- NIHR [RP-PG-0407-10371]
- EU-FP7 (EpiMigrant) [279143]
- Action on Hearing Loss [G51]
- EU-FP7 (AtheroRemo) [201668]
- Tampere University Foundation
- Tampere University Hospital Medical Funds [9M048, 9N035]
- Emil Aaltonen Foundation
- Finnish Foundation of Cardiovascular Research
- Pirkanmaa Regional Fund of the Finnish Cultural Foundation
- Yrjo Jahnsson Foundation
- Tampere Tuberculosis Foundation
- Signe and Ane Gyllenberg Foundation
- Diabetes Research Foundation of the Finnish Diabetes Association
- NIHR-BRC Cambridge
- European Research Council (ERC) [268834]
- Pfizer
- Merck
- Biogen
- University of Cambridge
- ERC [268834]
- Estonian Research Council
- EPIC-CVD Coordinating Centre team
- European Research Council (ERC) [268834] Funding Source: European Research Council (ERC)
- British Heart Foundation [PG/12/32/29544, RG/08/014/24067, FS/14/76/30933, RG/10/12/28456, RG/15/12/31616, FS/12/80/29821, RG/14/5/30893] Funding Source: researchfish
- Medical Research Council [G0601966, G0700931, G0800270, MC_qA137853, MR/L003120/1] Funding Source: researchfish
- National Institute for Health Research [CL-2011-11-003, NF-SI-0512-10165, NF-SI-0515-10091, NF-SI-0611-10170] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15SA0018486] Funding Source: researchfish
- MRC [G0601966, G0800270, G0700931, MR/L003120/1, MR/N011775/1] Funding Source: UKRI
Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 x 10(-8)) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1-4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n(cases) = 10,801) as well as a stricter definition without angina (HARD; n(cases) = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS(2,3). This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold(2), thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.
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