ArticleNature genetics2025
Large-scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy.
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Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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45citing papers in PubMed, 2 pooled it
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction.Nature genetics · 2026Pooled it
- Genome-wide analysis identifies susceptibility loci for heart failure and nonischemic cardiomyopathy subtype in the East Asian populations.PLoS genetics · 2025Pooled it
- Unlocking the Regulatory Genome: Interpreting the Clinical Impact of Noncoding Variants in Genetic Cardiomyopathies.Circulation. Genomic and precision medicine · 2026Review
- Clinical utility of polygenic risk scores in cardiovascular disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Four-dimensional left ventricular motion clustering reveals cardiovascular phenotypes at population scale.Scientific reports · 2026Article
- Beyond sarcomere genetics: proteomic insights into hypertrophic cardiomyopathy.Biophysical reviews · 2026Review
- Biobank-Scale Plasma Proteomics Identifies Novel Biomarkers in Hypertrophic Cardiomyopathy.Circulation. Genomic and precision medicine · 2026Article
- Genome and transcriptome-wide association studies identify multiple novel loci for dementia with grain in Japanese.Journal of human genetics · 2026Article
- An integrative single-nucleus multiomic atlas of the human left ventricle identifies gene regulatory network dynamics across cardiac development, aging, and disease.Genome biology · 2026Article
- Epigenetics, Modifiers, and Molecular Noise: Rethinking Pathophysiology in Dilated and Hypertrophic Cardiomyopathies.International journal of molecular sciences · 2026Review
- Revisiting the Genetics of Hypertrophic Cardiomyopathy: From Sarcomeres to Polygenic Modulation and Clinical Translation.Journal of clinical medicine · 2026Review
- Genomics of drug target prioritization for complex diseases.Nature reviews. Genetics · 2026Review
- EchoVisuALL: From Echocardiography to Gene Discovery.bioRxiv : the preprint server for biology · 2026Article
- Association of DNA methylation with hypertension and blood pressure: a 7-year longitudinal study from KORA F4/FF4.BMC medicine · 2026Article
- Single-Cell Multi-Omics Profiling of Human Septal Myectomy Tissue: Toward Precision Medicine in Obstructive Hypertrophic Cardiomyopathy.Journal of personalized medicine · 2026Review
- Polygenic Background and Penetrance of Pathogenic Variants in Hypertrophic and Dilated Cardiomyopathies.JAMA cardiology · 2026Article
- Genetic and Clinical Characterization of a South-Brazilian Hypertrophic Cardiomyopathy Cohort.Arquivos brasileiros de cardiologia · 2026Observational
- Leveraging the shared and opposing genetic mechanisms in the heritable cardiomyopathies.Research square · 2026Article
- Integration of dilated cardiomyopathy genomics with transcriptomics from the human heart implicates regulatory molecular mechanisms.medRxiv : the preprint server for health sciences · 2026Article
- Hypertrophic Cardiomyopathy is a Disease of Sarcomere Proteins.Methodist DeBakey cardiovascular journal · 2026Review
Corrections and comments
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Authors and funding
64 authors.
Rafik Tadros *Cardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada. rafik.tadros@umontreal.ca.ORCID http://orcid.org/0000-0002-1472-0258
Sean L Zheng *National Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-5762-6392
Christopher GraceDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Paloma JordàCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-9236-1713
Catherine FrancisNational Heart and Lung Institute, Imperial College London, London, UK.
Dominique M WestDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Sean J JurgensDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-1605-9782
Kate L ThomsonDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.ORCID http://orcid.org/0000-0003-2807-3431
Andrew R HarperDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.ORCID http://orcid.org/0000-0001-5327-0328
Elizabeth OrmondroydDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.ORCID http://orcid.org/0000-0002-9116-4064
Xiao XuMRC Laboratory of Medical Sciences, Imperial College London, London, UK.
Pantazis I TheotokisNational Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-8718-230X
Rachel J BuchanNational Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-2490-9289
Kathryn A McGurkNational Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-5445-6906
Francesco MazzarottoNational Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-6159-9980
Beatrice BoschiGenetics Unit, Careggi University Hospital, Florence, Italy.
Elisabetta PeloGenetics Unit, Careggi University Hospital, Florence, Italy.
Michael LeeNational Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-0186-4439
Michela NosedaNational Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-9553-5029
Amanda VarnavaNational Heart and Lung Institute, Imperial College London, London, UK.
Alexa M C VermeerDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Roddy WalshDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-5092-8825
Ahmad S AminDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-1600-7907
Marjon A van SlegtenhorstDepartment of Clinical Genetics, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Nicole M RoslinProgram in Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-4609-8299
Lisa J StrugProgram in Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-0503-9740
Erika SalviNeuroalgology Unit, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy.ORCID http://orcid.org/0000-0002-2724-2291
Chiara LanzaniGenomics of Renal Diseases and Hypertension Unit and Nephrology Operative Unit, IRCCS San Raffaele Hospital, Milan, Italy.
Antonio de MarvaoMRC Laboratory of Medical Sciences, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-9095-5887
Hypergenes InterOmics Collaborators
Jason D RobertsDepartment of Medicine, Section of Cardiac Electrophysiology, Division of Cardiology, Western University, London, Ontario, Canada.
Maxime Tremblay-GravelCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.
Genevieve GiraldeauCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.
Julia Cadrin-TourignyCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.
Philippe L L'AllierCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.
Patrick GarceauCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.
Mario TalajicCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.
Sarah A Gagliano TaliunCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-1306-1868
Yigal M PintoDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-2836-571X
Harry RakowskiDivision of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
Antonis PantazisRoyal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Wenjia BaiDepartment of Computing, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-2943-7698
John BaksiNational Heart and Lung Institute, Imperial College London, London, UK.
Brian P HallidayNational Heart and Lung Institute, Imperial College London, London, UK.
Sanjay K PrasadNational Heart and Lung Institute, Imperial College London, London, UK.
Paul J R BartonNational Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-1165-7767
Declan P O'ReganMRC Laboratory of Medical Sciences, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-0691-0270
Stuart A CookMRC Laboratory of Medical Sciences, Imperial College London, London, UK.
Rudolf A de BoerDepartment of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-4775-9140
Imke ChristiaansDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0001-5799-2344
Michelle MichelsEuropean Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARD-HEART), Amsterdam, the Netherlands.
Christopher M KramerDepartment of Medicine, Cardiovascular Division, University of Virginia Health, Charlottesville, VA, USA.
Carolyn Y HoCardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7334-7924
Stefan NeubauerRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, NIHR Oxford Biomedical Research Centre, Oxford, UK.
HCMR Investigators
Paul M MatthewsDepartment of Brain Sciences, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-1619-8328
Arthur A M WildeDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Jean-Claude TardifCardiovascular Genetics Centre and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-8200-8983
Iacopo OlivottoMeyer Children's Hospital IRCCS, Florence, Italy.
Arnon AdlerDivision of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
Anuj Goel *Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
James S Ware *National Heart and Lung Institute, Imperial College London, London, UK. j.ware@imperial.ac.uk.ORCID http://orcid.org/0000-0002-6110-5880
Connie R Bezzina *Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. c.r.bezzina@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-0633-3514
Hugh Watkins *Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. hugh.watkins@rdm.ox.ac.uk.ORCID http://orcid.org/0000-0002-5287-9016
Funding
HCMR Novel Markers of Prognosis in Hypertrophic CardiomyopathyU01HL117006 · NHLBI · UNIVERSITY OF VIRGINIA · PI KRAMER, CHRISTOPHER M., NEUBAUER, STEFAN · 2013 to 2017
$14.5MBritish Heart Foundation (BHF) BBC/F/21/220106British Heart Foundation (BHF) FS/15/81/31817British Heart Foundation (BHF) FS/ICRF/21/26019British Heart Foundation (BHF) RE/18/4/34215British Heart Foundation (BHF) RG/18/9/33887British Heart Foundation (BHF) RG/19/6/34387Hartstichting (Dutch Heart Foundation) 2020B005NHLBI NIH HHS U01 HL117006U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) U01HL117006-01A1Wellcome Trust
Abstract
Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. Here, we report results from a large genome-wide association study and multitrait analysis including 5,900 HCM cases, 68,359 controls and 36,083 UK Biobank participants with cardiac magnetic resonance imaging. We identified 70 loci (50 novel) associated with HCM and 62 loci (20 novel) associated with relevant left ventricular traits. Among the prioritized genes in the HCM loci, we identify a novel HCM disease gene, SVIL, which encodes the actin-binding protein supervillin, showing that rare truncating SVIL variants confer a roughly tenfold increased risk of HCM. Mendelian randomization analyses support a causal role of increased left ventricular contractility in both obstructive and nonobstructive forms of HCM, suggesting common disease mechanisms and anticipating shared response to therapy. Taken together, these findings increase our understanding of the genetic basis of HCM, with potential implications for disease management.
Indexed as
Cardiomyopathy, HypertrophicGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyMembrane ProteinsCase-Control StudiesFemaleHumansMaleMendelian Randomization AnalysisMicrofilament ProteinsMiddle AgedPolymorphism, Single NucleotideMembrane ProteinsMicrofilament Proteins
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