The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function
Open accessAbstract
BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING: For detailed information per study, see Acknowledgments.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“In addition to CAVS, a GWA study also found at a genome-wide significance level an association between rs6702619 and aortic root diameter (Wild et al., 2017).”
From Enhancer-associated aortic valve stenosis risk locus 1p21.2 alters NFATC2 binding site and promotes fibrogenesis (2021) · cites this paper as Wild et al., 2017
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
GCTA: a tool for genome-wide complex trait analysis
Yang, J., Lee, S. H., Goddard, M. E., & Visscher, P. M. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.11.011 · Cited by 8,279
LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bulik-Sullivan, B. K., Loh, P.-R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., Daly, M. J., Price, A. L., & Neale, B. M. (2015) · Nature Genetics · doi:10.1038/ng.3211 · Cited by 5,559
METAL: fast and efficient meta-analysis of genomewide association scans
Willer, C. J., Li, Y., & Abecasis, G. R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq340 · Cited by 5,205
Recommendations for chamber quantification☆
Lang, R. M., Bierig, M., Devereux, R. B., Flachskampf, F. A., Foster, E., Pellikka, P. A., Picard, M. H., Roman, M. J., Seward, J. B., & Shanewise, J. S. (2006) · European Journal of Echocardiography · doi:10.1016/j.euje.2005.12.014 · Cited by 3,588
Burden of Systolic and Diastolic Ventricular Dysfunction in the Community
Redfield, M. M., Jacobsen, S. J., Burnett, J. C. J., Mahoney, D. W., Bailey, K. R., & Rodeheffer, R. J. (2003) · JAMA · doi:10.1001/jama.289.2.194 · Cited by 2,989
A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease
the CARDIoGRAMplusC4D Consortium (2015) · Nature Genetics · doi:10.1038/ng.3396 · Cited by 2,447
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
The International Consortium for Blood Pressure Genome-Wide Association Studies (2011) · Nature · doi:10.1038/nature10405 · Cited by 2,033
Self-citationRegulation of cardiac hypertrophy by intracellular signalling pathways
Heineke, J., & Molkentin, J. D. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1983 · Cited by 1,890
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
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., et al. (2011) · Nature Genetics · doi:10.1038/ng.784 · Cited by 1,866
Self-citation
Cited by
Sorted by citations
Shah, S. H., Henry, A., Roselli, C., Lin, H., Sveinbjörnsson, G., Fatemifar, G., Hedman, Å. K., Wilk, J. B., Morley, M. P., Chaffin, M. D., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13690-5 · Cited by 836
Self-citationNitric oxide signalling in cardiovascular health and disease
Farah, C., Michel, L. Y. M., & Balligand, J.-L. (2018) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.224 · Cited by 779
Objectives, design and main findings until 2020 from the Rotterdam Study
Ikram, M. A., Brusselle, G., Ghanbari, M., Goedegebure, A., Ikram, M. K., Kavousi, M., Kieboom, B. C. T., Klaver, C. C. W., de Knegt, R. J., Luik, A. I., et al. (2020) · European Journal of Epidemiology · doi:10.1007/s10654-020-00640-5 · Cited by 463
Self-citationGoette, A., Corradi, D., Dobrev, D., Aguinaga, L., Cabrera, J. Á., Chugh, S. S., de Groot, J. R., Soulat-Dufour, L., Fenelon, G., Hatem, S. N., et al. (2024) · EP Europace · doi:10.1093/europace/euae204 · Cited by 370
Pirruccello, J. P., Bick, A., Wang, M., Chaffin, M., Friedman, S., Yao, J., Guo, X., Venkatesh, B. A., Taylor, K. D., Post, W. S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15823-7 · Cited by 267
Self-citation
Metadata
- Authors
- Wild, P. S., Felix, J. F., Schillert, A., Teumer, A., Chen, M.-H., Leening, M. J. G., Völker, U., Großmann, V., Brody, J. A., Irvin, M. R., Shah, S. J., Pramana, S., Lieb, W., Schmidt, R., Stanton, A. V., Malzahn, D., Smith, A. V., Sundström, J., Minelli, C., Ruggiero, D., Lyytikäinen, L.-P., Tiller, D., Smith, J. G., Monnereau, C., Di Tullio, M. R., Musani, S. K., Morrison, A. C., Pers, T. H., Morley, M., Kleber, M. E., Aragam, J., Benjamin, E. J., Bis, J. C., Bisping, E., Broeckel, U., Cheng, S., Deckers, J. W., Del Greco M, F., Edelmann, F., Fornage, M., Franke, L., Friedrich, N., Harris, T. B., Hofer, E., Hofman, A., Huang, J., Hughes, A. D., Kähönen, M., investigators, K., Kruppa, J., Lackner, K. J., Lannfelt, L., Laskowski, R., Launer, L. J., Leosdottir, M., Lin, H., Lindgren, C. M., Loley, C., MacRae, C. A., Mascalzoni, D., Mayet, J., Medenwald, D., Morris, A. P., Müller, C., Müller-Nurasyid, M., Nappo, S., Nilsson, P. M., Nuding, S., Nutile, T., Peters, A., Pfeufer, A., Pietzner, D., Pramstaller, P. P., Raitakari, O. T., Rice, K. M., Rivadeneira, F., Rotter, J. I., Ruohonen, S. T., Sacco, R. L., Samdarshi, T. E., Schmidt, H., Sharp, A. S. P., Shields, D. C., Sorice, R., Sotoodehnia, N., Stricker, B. H., Surendran, P., Thom, S., Töglhofer, A. M., Uitterlinden, A. G., Wachter, R., Völzke, H., Ziegler, A., Münzel, T., März, W., Cappola, T. P., Hirschhorn, J. N., Mitchell, G. F., Smith, N. L., Fox, E. R., Dueker, N. D., Jaddoe, V. W. V., Melander, O., Russ, M., Lehtimäki, T., Ciullo, M., Hicks, A. A., Lind, L., Gudnason, V., Pieske, B., Barron, A. J., Zweiker, R., Schunkert, H., Ingelsson, E., Liu, K., Arnett, D. K., Psaty, B. M., Blankenberg, S., Larson, M. G., Felix, S. B., Franco, O. H., Zeller, T., Vasan, R. S., & Dörr, M.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Erasmus MC (NL)
- German Centre for Cardiovascular Research (DE)
- Universitätsmedizin Greifswald (DE)
- Boston University (US)
- University of Washington (US)
- University of Alabama at Birmingham (US)
- Northwestern University (US)
- Karolinska Institutet (SE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Medical University of Graz (AT)
- Royal College of Surgeons in Ireland (IE)
- Universitätsmedizin Göttingen (DE)
- University of Iceland (IS)
- Uppsala University (SE)
- Imperial College London (GB)
- Institute of Genetics and Biophysics (IT)
- Tampere University (FI)
- Martin Luther University Halle-Wittenberg (DE)
- Broad Institute (US)
- University of Veterinary Medicine Hannover, Foundation (DE)
- National Institutes of Health (US)
- Hammersmith Hospital (GB)
- Centre for Human Genetics (GB)
- Universität Hamburg (DE)
- Lund University (SE)
- University of Turku (FI)
- The Lundquist Institute (US)
- Beaumont Hospital (IE)
- ORCID
- Wild, Philipp S.
- Felix, Janine F.
- Schillert, Arne
- Teumer, Alexander
- Chen, Ming-Huei
- Leening, Maarten J.G.
- Völker, Uwe
- Brody, Jennifer A.
- Irvin, Marguerite R.
- Shah, Sanjiv J.
- Pramana, Setia
- Lieb, Wolfgang
- Schmidt, Reinhold
- Stanton, Alice V.
- Smith, Albert Vernon
- Sundström, Johan
- Minelli, Cosetta
- Ruggiero, Daniela
- Lyytikäinen, Leo-Pekka
- Monnereau, Claire
- Morrison, Alanna C.
- Pers, Tune H.
- Morley, Michael
- Kleber, Marcus E.
- Benjamin, Emelia J.
- Bis, Joshua C.
- Bisping, Egbert
- Broeckel, Ulrich
- Cheng, Susan
- Deckers, Jaap W.
- Edelmann, Frank
- Fornage, Myriam
- Franke, Lude
- Harris, Tamara B.
- Hofer, Edith
- Huang, Jie
- Hughes, Alun D.
- Kähönen, Mika
- Kruppa, Jochen
- Lackner, Karl J.
- Launer, Lenore J.
- Leosdottir, Margrét
- Lin, Honghuang
- Lindgren, Cecilia M.
- MacRae, Calum A.
- Mascalzoni, Deborah
- Mayet, Jamil
- Medenwald, Daniel
- Morris, Andrew P.
- Müller, Christian
- Nappo, Stefania
- Nilsson, Peter M.
- Nuding, Sebastian
- Nutile, Teresa
- Peters, Annette
- Pramstaller, Peter P.
- Raitakari, Olli T.
- Rice, Kenneth M.
- Rivadeneira, Fernando
- Rotter, Jerome I.
- Ruohonen, Saku T.
- Sacco, Ralph L.
- Schmidt, Helena
- Sharp, Andrew S.P.
- Stricker, Bruno H.
- Surendran, Praveen
- Thom, Simon
- Uitterlinden, André G.
- Wachter, Rolf
- Völzke, Henry
- Ziegler, Andreas
- Münzel, Thomas
- März, Winfried
- Cappola, Thomas P.
- Hirschhorn, Joel N.
- Mitchell, Gary F.
- Smith, Nicholas L.
- Dueker, Nicole D.
- Jaddoe, Vincent W.V.
- Melander, Olle
- Russ, Martin
- Lehtimäki, Terho
- Ciullo, Marina
- Hicks, Andrew A.
- Lind, Lars
- Gudnason, Vilmundur
- Pieske, Burkert
- Barron, Anthony J.
- Zweiker, Robert
- Schunkert, Heribert
- Ingelsson, Erik
- Liu, Kiang
- Arnett, Donna K.
- Psaty, Bruce M.
- Blankenberg, Stefan
- Larson, Martin G.
- Felix, Stephan B.
- Franco, Oscar H.
- Zeller, Tanja
- Vasan, Ramachandran S.
- Dörr, Marcus
- Venue
- Journal of Clinical Investigation
- Published
- 2017-04-10
- Volume
- 127
- Issue
- 5
- Pages
- 1798-1812
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5409098
- OpenAlex
- W2604500500
- Cited by
- 129
- References
- 54
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 10 · 2023: 7 · 2022: 18 · 2021: 15 · 2020: 18 · 2019: 21 · 2018: 15 · 2017: 4
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Open Research (University of Surrey) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Apollo
- Funders
- Northwestern University (HHSN268201300027C, HHSN268201300028C, HHSN268200900041C, HHSN268201300026C, HHSN268201300025C, HHSN268201300029C)
- University of Minnesota (HHSN268201300025C, HHSN268201300029C, HHSN268201300028C, HHSN268201300026C, HHSN268200900041C, HHSN268201300027C)
- School of Medicine, Boston University
- Foundation for Cardiovascular Research
- Johns Hopkins University (HHSN268200900041C)
- University of Alabama at Birmingham (HHSN268201300027C, HHSN268201300026 C, HHSN268201300028C, HHSN268201300025C and HHSN268201300026C, HHSN268201300029C, HHSN268200900041C, HHSN268201300025C)
- Yrjö Jahnssonin Säätiö
- University of Alabama (HHSN268201300026 C, HHSN268201300025C)
- National Institute for Health and Care Research (NF-SI-0512-10165)
- British Heart Foundation (RG/13/13/30194, RG/08/014/24067)
- European Commission (018947, 201668, 01ZZ0103, 286284, 305739, 01ZZ0403, 03ZIK012, 01ZZ9603, LSHG-CT-2006-018947)
- Deutsche Forschungsgemeinschaft (01ZZ0403, 01ZZ9603, 03ZIK012, 01EO1003, 01ZZ0103)
- Stiftelsen för Strategisk Forskning (ICA08-0047)
- ZonMw (BMBF 01EO1003, 050-060-810)
- Kela
- Bundesministerium für Bildung und Forschung (01ZZ9603, 01ZZ0103, and 01ZZ0403, BMBF 01EO1003, 03ZIK012, 01ZZ0403, and 01ZZ0403, 01GS0837, 01EO1003, 01GS0422, 01ZZ0103, 01ZZ9603)
- Austrian Science Fund
- Suomen Kulttuurirahasto
- Crafoordska Stiftelsen
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (050.060.810, 911-03-012, 175.010.200, 175.010.2005.011)
- Lunds Universitet
- Lundbeckfonden (R190 2014-3904)
- Hjärt-Lungfonden (20120197)
- Juho Vainion Säätiö
- Signe ja Ane Gyllenbergin Säätiö
- Vetenskapsrådet (70374401, 80576801, 2012-01397)
- Emil Aaltosen Säätiö (286284, 201668, X51001)
- Akademiska Sjukhuset
- Sydäntutkimussäätiö (121584, 286284, 124282, X51001, 134309, 126925, 201668, 129378, 117787, 41071)
- Tampereen Tuberkuloosisäätiö (286284, 201668, X51001)
- Uppsala Universitet
- Svenska Läkaresällskapet
- Diabetesliitto
- Paavo Nurmen Säätiö
- Science for Life Laboratory
- Novo Nordisk Fonden (NNF16OC0021496)
- Skånes universitetssjukhus
- Provincia autonoma di Bolzano - Alto Adige
- National Institutes of Health (HHSN268200900041C, n01hc085082-026, n01hc085081-021, HHSN268201300026C, HHSN268201300028C, n01hc085079-024, HHSN268201300027C, n01hc085084-005, 1r01hl120393-01a1, HHSN268201300025C, n01hc085083-027, n01hc085080-026, UL1TR000124, n01hc085086-022, 201668, HHSN268201300050C, 305739, HHSN268201300029C, 01EO1003, 5u01hl054472-10, n01hc25195-41-0-1, n01hc55222-0-0-0, n01hc035129-010, HHSN 268201300048C, R24OD017870)
- Kaiser Foundation Research Institute (HHSN268201300029C, HHSN268201300028C, HHSN268200900041C, HHSN268201300025C, HHSN268201300026C, U01-HG004729, HHSN268201300027C)
- Medical Research Council (MR/L003120/1)
- European Regional Development Fund
- Helmholtz Zentrum München
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz
- National Institute on Aging (HHSN268201300029C, HHSN268201300026C, HHSN268201300025C, HHSN268201300028C, R01AG023629, HHSN268200900041C, HHSN268201300027C)
- National Heart, Lung, and Blood Institute (HHSN268201300050C, HHSN268201300028C, U10HL054497, N01 HC085086, HHS-N2-68201300029C, HHSN268201300027C, U01-HL054472, N01 HC085079, R01-HL120393, N01 HC085083, HHSN268201500001I, U10HL054509, U01HL054495, U01HL054497, N01 HC085080, R01HL087652, R01HL103612, HHSN268200900041C, HHSN 268200800007C, N01 HC035129, HHSN268201300048C, HHSN268201500001C, U10HL054473, U01HL054496, U10HL054471, R01HL093328, U01HL130114, HHSN268201300026C, U01HL054471, HHS-N2-68201300025C, HHSN268201300049C, N01-HC-025195, HHSN268201200036C, R01HL107385, U10HL054495, N01HC085082, R01HL105756, U01HL080295, N01 HC055222, R01 HL, R00HL107642, U01HL054509, N01 HC085081, HHSN268201300047C, U01HL054473, R01HL126136, R01HL105993, U10HL054472, N01 HC085084, R01HL055673, R01HL131532, U10HL054496)
- National Human Genome Research Institute (U01HG04424, U01HG004446, U01HG004729, U01HG004424, HG004446)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063491, P30DK079626)
- National Institute of Neurological Disorders and Stroke (Z01NS002993, HHSN268200900041C, HHSN268201300028C, HHSN268201300026C, R01NS036286, HHSN268201300025C, HHSN268201300029C, R01 NS-36286, HHSN268201300027C)
- National Center for Advancing Translational Sciences
- National Institute on Minority Health and Health Disparities (HHSN268201300050C, HHSN268201300048C)
- Interreg
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- cardiac structure, cardiac function, left ventricular function, diastolic function, systolic function, aortic root diameter, genetic variants, single nucleotide polymorphisms, MTSS1, ATXN2, CACNA1C, TMEM16A
- MeSH terms
- Female, Heart Diseases, Humans, Male, Myocardium, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci
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 ›
Are you an author, or do you see a problem with this page? Request a review
