Large-scale association analysis identifies new risk loci for coronary artery disease
Open accessAbstract
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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Genomewide association analyses since 2007 have identified more than 50 independent loci associated with coronary artery disease risk.
“Since 2007, genomewide association analyses have identified more than 50 independent loci associated with the risk of coronary artery disease.7–15”
From Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease (2016) · cites this paper as [14]
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- Authors
- The CARDIoGRAMplusC4D Consortium, Deloukas, P., DIAGRAM Consortium, CARDIOGENICS Consortium, MuTHER Consortium, Wellcome Trust Case Control Consortium, Kanoni, S., Willenborg, C., Farrall, M., Assimes, T. L., Thompson, J. R., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, B. A., Stirrups, K., König, I. R., Cazier, J.-B., Johansson, Å., Hall, A. S., Lee, J.-Y., Willer, C. J., Chambers, J. C., Esko, T., Folkersen, L., Goel, A., Grundberg, E., Havulinna, A. S., Ho, W. K., Hopewell, J. C., Eriksson, N., Kleber, M. E., Kristiansson, K., Lundmark, P., Lyytikäinen, L.-P., Rafelt, S., Shungin, D., Strawbridge, R. J., Thorleifsson, G., Tikkanen, E., Van Zuydam, N., Voight, B. F., Waite, L. L., Zhang, W., Ziegler, A., Absher, D., Altshuler, D., Balmforth, A. J., Barroso, I., Braund, P. S., Burgdorf, C., Claudi-Boehm, S., Cox, D., Dimitriou, M., Do, R., Doney, A. S. F., Mokhtari, N. E., Eriksson, P., Fischer, K., Fontanillas, P., Franco-Cereceda, A., Gigante, B., Groop, L., Gustafsson, S., Hager, J., Hallmans, G., Han, B.-G., Hunt, S. E., Kang, H. M., Illig, T., Kessler, T., Knowles, J. W., Kolovou, G., Kuusisto, J., Langenberg, C., Langford, C., Leander, K., Lokki, M.-L., Lundmark, A., McCarthy, M. I., Meisinger, C., Melander, O., Mihailov, E., Maouche, S., Morris, A. D., Müller-Nurasyid, M., Nikus, K., Peden, J. F., Rayner, N. W., Rasheed, A., Rosinger, S., Rubin, D., Rumpf, M. P., Schäfer, A., Sivananthan, M., Song, C., Stewart, A. F. R., Tan, S.-T., Thorgeirsson, G., Schoot, C. E. V. D., Wagner, P. J., Wells, G. A., Wild, P. S., Yang, T.-P., Amouyel, P., Arveiler, D., Basart, H., Boehnke, M., Boerwinkle, E., Brambilla, P., Cambien, F., Cupples, A. L., de Faire, U., Dehghan, A., Diemert, P., Epstein, S. E., Evans, A., Ferrario, M. M., Ferrières, J., Gauguier, D., Go, A. S., Goodall, A. H., Gudnason, V., Hazen, S. L., Holm, H., Iribarren, C., Jang, Y., Kähönen, M., Kee, F., Kim, H.-S., Klopp, N., Koenig, W., Kratzer, W., Kuulasmaa, K., Laakso, M., Laaksonen, R., Lee, J.-Y., Lind, L., Ouwehand, W. H., Parish, S., Park, J. E., Pedersen, N. L., Peters, A., Quertermous, T., Rader, D. J., Salomaa, V., Schadt, E., Shah, S. H., Sinisalo, J., Stark, K., Stefansson, K., Trégouët, D.-A., Virtamo, J., Wallentin, L., Wareham, N., Zimmermann, M. E., Nieminen, M. S., Hengstenberg, C., Sandhu, M. S., Pastinen, T., Syvänen, A.-C., Hovingh, G. K., Dedoussis, G., Franks, P. W., Lehtimäki, T., Metspalu, A., Zalloua, P. A., Siegbahn, A., Schreiber, S., Ripatti, S., Blankenberg, S. S., Perola, M., Clarke, R., Boehm, B. O., O'Donnell, C., Reilly, M. P., März, W., Collins, R., Kathiresan, S., Hamsten, A., Kooner, J. S., Thorsteinsdottir, U., Danesh, J., Palmer, C. N. A., Roberts, R., Watkins, H., Schunkert, H., & Samani, N. J.
- Affiliations
- Wellcome Sanger Institute (GB)
- Institute for Integrative and Experimental Genomics (DE)
- Centre for Human Genetics (GB)
- Stanford Medicine (US)
- University of Leicester (GB)
- Karolinska Institutet (SE)
- University of Cambridge (GB)
- University of Lübeck (DE)
- University of Oxford (GB)
- Uppsala University (SE)
- University of Leeds (GB)
- Korea National Institute of Health (KR)
- University of Michigan (US)
- Imperial College London (GB)
- University of Tartu (EE)
- Karolinska University Hospital (SE)
- King's College London (GB)
- Finnish Institute for Health and Welfare (FI)
- University of Pennsylvania (US)
- Heidelberg University (DE)
- Tampere University (FI)
- Lund University (SE)
- University of Helsinki (FI)
- HudsonAlpha Institute for Biotechnology (US)
- Broad Institute (US)
- Deutsches Herzzentrum München (DE)
- University Hospital Ulm (DE)
- Pfizer (United States) (US)
- Harokopio University of Athens (GR)
- University of Dundee (GB)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Umeå University (SE)
- Medizinische Hochschule Hannover (DE)
- Onassis Cardiac Surgery Center (GR)
- University of Eastern Finland (FI)
- Addenbrooke's Hospital (GB)
- Helmholtz Munich (DE)
- Inserm (FR)
- Tampere University Hospital (FI)
- Christian-Albrechts-Universität zu Kiel (DE)
- University of Ottawa (CA)
- Hammersmith Hospital (GB)
- Sanquin (NL)
- Johannes Gutenberg University Mainz (DE)
- Université de Strasbourg (FR)
- Amsterdam UMC Location University of Amsterdam (NL)
- The University of Texas Health Science Center at Houston (US)
- University of Milano-Bicocca (IT)
- Erasmus MC (NL)
- Universität Hamburg (DE)
- MedStar Washington Hospital Center (US)
- Queen's University Belfast (GB)
- Hôpital Rangueil (FR)
- Kaiser Permanente (US)
- Cleveland Clinic (US)
- Yonsei University (KR)
- Seoul National University (KR)
- National Health Service (GB)
- Samsung Medical Center (KR)
- Icahn School of Medicine at Mount Sinai (US)
- Duke University (US)
- Helsinki University Hospital (FI)
- McGill University (CA)
- Harvard University (US)
- Lebanese American University (LB)
- Corresponding author
- Deloukas, Panos
- Samani, Nilesh J
- ORCID
- Deloukas, Panos
- Kanoni, Stavroula
- Farrall, Martin
- Assimes, Themistocles L
- Ingelsson, Erik
- Saleheen, Danish
- Erdmann, Jeanette
- Goldstein, Benjamin A
- Stirrups, Kathleen
- König, Inke R
- Cazier, Jean-Baptiste
- Johansson, Åsa
- Hall, Alistair S
- Lee, Jong-Young
- Willer, Cristen J
- Chambers, John C
- Esko, Tõnu
- Folkersen, Lasse
- Goel, Anuj
- Grundberg, Elin
- Havulinna, Aki S
- Ho, Weang K
- Hopewell, Jemma C
- Eriksson, Niclas
- Kleber, Marcus E
- Kristiansson, Kati
- Lundmark, Per
- Lyytikäinen, Leo-Pekka
- Shungin, Dmitry
- Strawbridge, Rona J
- Tikkanen, Emmi
- Voight, Benjamin F
- Zhang, Weihua
- Ziegler, Andreas
- Absher, Devin
- Altshuler, David
- Barroso, Inês
- Braund, Peter S
- Burgdorf, Christof
- Cox, David
- Dimitriou, Maria
- Do, Ron
- Doney, Alex S F
- Eriksson, Per
- Fischer, Krista
- Fontanillas, Pierre
- Gigante, Bruna
- Gustafsson, Stefan
- Hager, Jörg
- Hallmans, Göran
- Hunt, Sarah E
- Kang, Hyun M
- Kessler, Thorsten
- Knowles, Joshua W
- Kolovou, Genovefa
- Kuusisto, Johanna
- Langenberg, Claudia
- Langford, Cordelia
- Leander, Karin
- Lokki, Marja-Liisa
- Lundmark, Anders
- McCarthy, Mark I
- Meisinger, Christa
- Melander, Olle
- Maouche, Seraya
- Morris, Andrew D
- Nikus, Kjell
- Rayner, N William
- Song, Ci
- Stewart, Alexandre F R
- Schoot, C Ellen van der
- Wells, George A
- Wild, Philipp S
- Yang, Tsun-Po
- Amouyel, Philippe
- Boehnke, Michael
- Boerwinkle, Eric
- Brambilla, Paolo
- Dehghan, Abbas
- Ferrières, Jean
- Gauguier, Dominique
- Go, Alan S
- Goodall, Alison H
- Hazen, Stanley L
- Iribarren, Carlos
- Jang, Yangsoo
- Kähönen, Mika
- Kee, Frank
- Kim, Hyo-Soo
- Kratzer, Wolfgang
- Kuulasmaa, Kari
- Laakso, Markku
- Laaksonen, Reijo
- Lee, Ji-Young
- Lind, Lars
- Ouwehand, Willem H
- Parish, Sarah
- Pedersen, Nancy L
- Peters, Annette
- Quertermous, Thomas
- Rader, Daniel J
- Salomaa, Veikko
- Schadt, Eric
- Shah, Svati H
- Sinisalo, Juha
- Stark, Klaus
- Trégouët, David-Alexandre
- Wallentin, Lars
- Wareham, Nicholas
- Zimmermann, Martina E
- Nieminen, Markku S
- Hengstenberg, Christian
- Sandhu, Manjinder S
- Pastinen, Tomi
- Hovingh, G Kees
- Dedoussis, George
- Franks, Paul W
- Lehtimäki, Terho
- Metspalu, Andres
- Zalloua, Pierre A
- Siegbahn, Agneta
- Schreiber, Stefan
- Ripatti, Samuli
- Blankenberg, Stefan S
- Perola, Markus
- Boehm, Bernhard O
- Reilly, Muredach P
- März, Winfried
- Collins, Rory
- Kathiresan, Sekar
- Hamsten, Anders
- Kooner, Jaspal S
- Danesh, John
- Roberts, Robert
- Watkins, Hugh
- Schunkert, Heribert
- Samani, Nilesh J
- Venue
- Nature Genetics
- Published
- 2012-12-02
- Volume
- 45
- Issue
- 1
- Pages
- 25-33
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3679547
- OpenAlex
- W2097572487
- Cited by
- 1,614
- References
- 37
- Citations by year
- 2026: 28 · 2025: 55 · 2024: 69 · 2023: 78 · 2022: 105 · 2021: 114 · 2020: 90 · 2019: 124 · 2018: 155 · 2017: 184 · 2016: 184 · 2015: 209 · 2014: 142 · 2013: 73 · 2012: 1
- FWCI
- 81.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- IrInSubria (University of Insubria) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Research Portal (Queen's University Belfast) (submittedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- University of Bern
- Wellcome Trust
- National Institute for Health and Care Research (NF-SI-0611-10170, RP-PG-0310-1002, NF-SI-0611-10099)
- British Heart Foundation (PG/08/094/26019, RG/08/014/24067, RG/09/012/28096)
- University of Oxford
- Queen's University Belfast
- Institut National de la Santé et de la Recherche Médicale
- Università degli Studi di Milano-Bicocca
- Queen's University
- Université de Strasbourg
- Université de Toulouse
- Université Pierre et Marie Curie
- Terveyden ja hyvinvoinnin laitos
- Medical Research Council (MC_UU_12015/1)
- National Heart, Lung, and Blood Institute (R00HL094535, K24HL107643, R01HL111694)
- Centre for Public Health, Queen's University Belfast
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020572, R01DK062370)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Keywords
- coronary artery disease, genetic susceptibility loci, genome-wide association study, lipid metabolism, inflammation, heritability, blood pressure, diabetes mellitus, candidate genes
- MeSH terms
- Adult, Aged, Cell Line, Coronary Artery Disease, Female, Humans, Male, Middle Aged, Risk Factors, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, White People, Asian People, Gene Regulatory Networks, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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