Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
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We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10⁻⁸ and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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In a genetic risk score analysis combining lead variants at all seven LTL-associated loci in 22,233 CAD cases and 64,762 controls, alleles associated with shorter LTL were associated with increased risk of CAD (21% (95% CI: 5-35%) per standard deviation in LTL, p=0.014).
“Moreover, a genetic risk score analysis combining lead variants at all seven loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of CAD (21% (95% CI: 5–35%) per standard deviation in LTL, p=0.014).”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [30]
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“The ABO blood group locus has shown significant associations for several phenotypes; rs651007 has a particularly strong effect on E-selectin 31 and has also been found in GWAS on low-density lipoprotein cholesterol 32 , coronary artery disease 33 and red blood cell count 25 .”
Self-citationMonogenic and Polygenic Models of Coronary Artery Disease
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Role of sGC-dependent NO signalling and myocardial infarction risk
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Self-citation
- Authors
- Cardiogenics, Schunkert, H., the CARDIoGRAM Consortium, König, I. R., Kathiresan, S., Reilly, M. P., Assimes, T. L., Holm, H., Preuss, M., Stewart, A. F. R., Barbalic, M., Gieger, C., Absher, D., Aherrahrou, Z., Allayee, H., Altshuler, D., Anand, S. S., Andersen, K., Anderson, J. L., Ardissino, D., Ball, S. G., Balmforth, A. J., Barnes, T. A., Becker, D. M., Becker, L. C., Berger, K., Bis, J. C., Boekholdt, S. M., Boerwinkle, E., Braund, P. S., Brown, M. J., Burnett, M. S., Buysschaert, I., Carlquist, J. F., Chen, L., Cichon, S., Codd, V., Davies, R. W., Dedoussis, G., Dehghan, A., Demissie, S., Devaney, J. M., Diemert, P., Do, R., Doering, A., Eifert, S., Mokhtari, N. E. E., Ellis, S. G., Elosua, R., Engert, J. C., Epstein, S. E., de Faire, U., Fischer, M., Folsom, A. R., Freyer, J., Gigante, B., Girelli, D., Gretarsdottir, S., Gudnason, V., Gulcher, J. R., Halperin, E., Hammond, N., Hazen, S. L., Hofman, A., Horne, B. D., Illig, T., Iribarren, C., Jones, G. T., Jukema, J. W., Kaiser, M. A., Kaplan, L. M., Kastelein, J. J. P., Khaw, K.-T., Knowles, J. W., Kolovou, G., Kong, A., Laaksonen, R., Lambrechts, D., Leander, K., Lettre, G., Li, M., Lieb, W., Loley, C., Lotery, A. J., Mannucci, P. M., Maouche, S., Martinelli, N., McKeown, P. P., Meisinger, C., Meitinger, T., Melander, O., Merlini, P. A., Mooser, V., Morgan, T., Mühleisen, T. W., Muhlestein, J. B., Münzel, T., Musunuru, K., Nahrstaedt, J., Nelson, C. P., Nöthen, M. M., Olivieri, O., Patel, R. S., Patterson, C. C., Peters, A., Peyvandi, F., Qu, L., Quyyumi, A. A., Rader, D. J., Rallidis, L. S., Rice, C., Rosendaal, F. R., Rubin, D., Salomaa, V., Sampietro, M. L., Sandhu, M. S., Schadt, E., Schäfer, A., Schillert, A., Schreiber, S., Schrezenmeir, J., Schwartz, S. M., Siscovick, D. S., Sivananthan, M., Sivapalaratnam, S., Smith, A., Smith, T. B., Snoep, J. D., Soranzo, N., Spertus, J. A., Stark, K., Stirrups, K., Stoll, M., Tang, W. H. W., Tennstedt, S., Thorgeirsson, G., Thorleifsson, G., Tomaszewski, M., Uitterlinden, A. G., van Rij, A. M., Voight, B. F., Wareham, N. J., Wells, G. A., Wichmann, H.-E., Wild, P. S., Willenborg, C., Witteman, J. C. M., Wright, B. J., Ye, S., Zeller, T., Ziegler, A., Cambien, F., Goodall, A. H., Cupples, L. A., Quertermous, T., März, W., Hengstenberg, C., Blankenberg, S., Ouwehand, W. H., Hall, A. S., Deloukas, P., Thompson, J. R., Stefansson, K., Roberts, R., Thorsteinsdottir, U., O'Donnell, C. J., McPherson, R., & Erdmann, J.
- Affiliations
- University of Lübeck (DE)
- Massachusetts General Hospital (US)
- Broad Institute (US)
- Stanford Medicine (US)
- deCODE Genetics (Iceland) (IS)
- Ottawa Heart Institute (CA)
- Helmholtz Munich (DE)
- HudsonAlpha Institute for Biotechnology (US)
- University of Southern California (US)
- Population Health Research Institute (CA)
- University of Iceland (IS)
- University of Utah (US)
- University of Leeds (GB)
- Johns Hopkins University (US)
- University of Washington (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- University of Leicester (GB)
- MedStar Washington Hospital Center (US)
- University of Bonn (DE)
- Harokopio University of Athens (GR)
- Erasmus MC (NL)
- Boston University (US)
- McGill University (CA)
- München Klinik (DE)
- Cleveland Clinic (US)
- University of Minnesota (US)
- Karolinska Institutet (SE)
- University of Verona (IT)
- International Computer Science Institute (US)
- Kaiser Permanente (US)
- Leiden University Medical Center (NL)
- University of Cambridge (GB)
- Onassis Cardiac Surgery Center (GR)
- Tampere University Hospital (FI)
- Montreal Heart Institute (CA)
- University of Pennsylvania (US)
- Southampton General Hospital (GB)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Queen's University Belfast (GB)
- TUM Klinikum (DE)
- Lund University (SE)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Vanderbilt University (US)
- Johannes Gutenberg University Mainz (DE)
- University of Milan (IT)
- Emory University (US)
- National and Kapodistrian University of Athens (GR)
- Finnish Institute for Health and Welfare (FI)
- Sage Bionetworks (US)
- Christian-Albrechts-Universität zu Kiel (DE)
- National Health Service (GB)
- National Institutes of Health (US)
- Wellcome Sanger Institute (GB)
- University of Missouri–Kansas City (US)
- University of Münster (DE)
- Queen Mary University of London (GB)
- Inserm (FR)
- Medical University of Graz (AT)
- NHS Blood and Transplant (GB)
- Corresponding author
- Schunkert, Heribert
- ORCID
- Schunkert, Heribert
- König, Inke R
- Kathiresan, Sekar
- Reilly, Muredach P
- Assimes, Themistocles L
- Preuss, Michael
- Stewart, Alexandre F R
- Gieger, Christian
- Aherrahrou, Zouhair
- Allayee, Hooman
- Altshuler, David
- Anand, Sonia S
- Andersen, Karl
- Anderson, Jeffrey L
- Ardissino, Diego
- Ball, Stephen G
- Becker, Diane M
- Becker, Lewis C
- Bis, Joshua C
- Boekholdt, S Matthijs
- Boerwinkle, Eric
- Braund, Peter S
- Brown, Morris J
- Buysschaert, Ian
- Cichon, Sven
- Codd, Veryan
- Dedoussis, George
- Dehghan, Abbas
- Demissie, Serkalem
- Devaney, Joseph M
- Do, Ron
- Ellis, Stephen G
- Engert, James C
- Fischer, Marcus
- Folsom, Aaron R
- Gigante, Bruna
- Girelli, Domenico
- Gudnason, Vilmundur
- Halperin, Eran
- Hazen, Stanley L
- Horne, Benjamin D
- Iribarren, Carlos
- Jones, Gregory T
- Jukema, J Wouter
- Kaplan, Lee M
- Kastelein, John J P
- Khaw, Kay-Tee
- Knowles, Joshua W
- Kolovou, Genovefa
- Kong, Augustine
- Laaksonen, Reijo
- Lambrechts, Diether
- Leander, Karin
- Lettre, Guillaume
- Li, Mingyao
- Lieb, Wolfgang
- Lotery, Andrew J
- Mannucci, Pier M
- Maouche, Seraya
- Martinelli, Nicola
- McKeown, Pascal P
- Meisinger, Christa
- Meitinger, Thomas
- Melander, Olle
- Mooser, Vincent
- Morgan, Thomas
- Muhlestein, Joseph B
- Münzel, Thomas
- Nelson, Christopher P
- Nöthen, Markus M
- Olivieri, Oliviero
- Patel, Riyaz S
- Patterson, Chris C
- Peters, Annette
- Peyvandi, Flora
- Qu, Liming
- Quyyumi, Arshed A
- Rader, Daniel J
- Rosendaal, Frits R
- Salomaa, Veikko
- Schadt, Eric
- Schillert, Arne
- Schreiber, Stefan
- Schrezenmeir, Jürgen
- Siscovick, David S
- Sivapalaratnam, Suthesh
- Smith, Albert
- Snoep, Jaapjan D
- Soranzo, Nicole
- Spertus, John A
- Stark, Klaus
- Stoll, Monika
- Tang, W H Wilson
- Tennstedt, Stephanie
- Tomaszewski, Maciej
- Voight, Benjamin F
- Wells, George A
- Wichmann, H-Erich
- Wild, Philipp S
- Ye, Shu
- Zeller, Tanja
- Ziegler, Andreas
- Goodall, Alison H
- Cupples, L Adrienne
- Quertermous, Thomas
- März, Winfried
- Blankenberg, Stefan
- Ouwehand, Willem H
- Hall, Alistair S
- Deloukas, Panos
- Roberts, Robert
- McPherson, Ruth
- Erdmann, Jeanette
- Venue
- Nature Genetics
- Published
- 2011-03-06
- Volume
- 43
- Issue
- 4
- Pages
- 333-338
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3119261
- OpenAlex
- W2112848098
- Cited by
- 1,866
- References
- 40
- Citations by year
- 2026: 36 · 2025: 58 · 2024: 91 · 2023: 82 · 2022: 92 · 2021: 101 · 2020: 112 · 2019: 109 · 2018: 145 · 2017: 154 · 2016: 175 · 2015: 182 · 2014: 141 · 2013: 152 · 2012: 163
- FWCI
- 17.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- PubMed Central (acceptedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- Leicester Research Archive (University of Leicester) (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)
- Research Explorer (The University of Manchester) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- OpenAgrar (submittedVersion)
- Funders
- British Heart Foundation (PG/08/094/26019, RG/08/014/24067, RG/09/012/28096)
- National Institutes of Health (n01hc25195-41-0-1)
- Economic and Social Research Council (ES/G007438/1)
- National Heart, Lung, and Blood Institute (R01HL087647, HL087647, N01-HC-025195, R01HL089650)
- 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, pleiotropy, cardiovascular risk factors, risk alleles, disease risk loci
- MeSH terms
- Adult, Aged, Alleles, Coronary Artery Disease, Female, Gene Frequency, Humans, Male, Middle Aged, Risk Factors, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, 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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