ArticleResearch square2026
Leveraging the shared and opposing genetic mechanisms in the heritable cardiomyopathies.
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Authors and funding
68 authors.
Daria R KramarenkoDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0001-6427-2521
Poeya HaydarlouDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.ORCID 0009-0000-3938-3377
George J PowellNational Heart and Lung Institute & MRC Laboratory of Medical Sciences, Imperial College London, London, UK.
Joel T RämöCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-6429-5149
Riyad JananNational Heart and Lung Institute & MRC Laboratory of Medical Sciences, Imperial College London, London, UK.
Claire PrinceNational Heart and Lung Institute & MRC Laboratory of Medical Sciences, Imperial College London, London, UK.
Dominic S ZimmermanDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.
Pantazis TheotokisNational Heart and Lung Institute & MRC Laboratory of Medical Sciences, Imperial College London, London, UK.ORCID 0000-0001-8718-230X
Prisca K ThamiNational Heart and Lung Institute & MRC Laboratory of Medical Sciences, Imperial College London, London, UK.
Jan HaasDepartment of Medicine III, Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, Heidelberg, Germany.
Sophie GarnierResearch Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics and Pathophysiology of Cardiovascular Disease, Sorbone Université, INSERM, Paris, France.ORCID 0000-0002-7492-1617
Frank RühleBioinformatics Core Facility, Institute of Molecular Biology gGmbH (IMB), Mainz, Germany.ORCID 0000-0001-7688-2394
Edwin PoelDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.
Amand F SchmidtDepartment of Clinical Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.
Sharlene DayUniversity of Pennsylvania, Philadelphia, PA, USA.
Adam HelmsDivision of Pediatric Cardiology, University of Michigan, Ann Arbor, MI.
Rachel LampertYale School of Medicine, New Haven, CT, USA.
Victoria ParikhStanford School of Medicine, Stanford, CA, USA.ORCID 0000-0002-5138-5559
Jodie InglesGarvan Institute of Medical Research, Sydney, NSW, Australia.
Iacopo OlivottoUniversity of Florence, Florence, Italy.
Neal LakdawalaCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Anjali OwensUniversity of Pennsylvania, Philadelphia, PA, USA.
Sara SaberiDivision of Pediatric Cardiology, University of Michigan, Ann Arbor, MI.
John StendhalYale School of Medicine, New Haven, CT, USA.
Euan AshleyStanford School of Medicine, Stanford, CA, USA.ORCID 0000-0001-9418-9577
Belinda GrayUniversity of Sydney, Sydney, NSW, Australia.
Mark W RussellDivision of Pediatric Cardiology, University of Michigan, Ann Arbor, MI.
Thomas D RyanCincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Joseph W RossanoChildren's Hospital of Philadelphia & University of Pennsylvania, Philadelphia, PA, USA.
Dominic AbramsBoston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Erin MillerCincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Kimberly LinChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Niccolo MauriziUniversity Hospital Lausanne (CHUV), Lausanne, Switzerland.
Alessia ArgiroUniversity of Florence, Florence, Italy.
Colin BerryGolden Jubilee National Hospital, Clydebank, Scotland, UK.
Rob CooperUniversity of Liverpool / Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
Andrew S FlettUniversity Hospital Southampton NHS Foundation Trust, Southampton, UK.
Roy S GardnerGolden Jubilee National Hospital, Clydebank, Scotland, UK.
John P GreenwoodBaker Heart and Diabetes Institute, Melbourne, Australia.ORCID 0000-0002-2861-0914
Brian P HallidayNational Heart and Lung Institute, Imperial College London, London, UK.
David HutchingsUniversity of Manchester, UK.
Masliza MahmodUniversity of Oxford, Oxford, UK.
Gerry P McCannDivision of Cardiovascular Sciences, University of Leicester, and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Stephen P PageLeeds Teaching Hospitals NHS Trust, Leeds, UK.
Charles PeeblesUniversity of Southampton, Southampton, UK.
Betty RamanUniversity of Oxford, Oxford, UK.
Peter SwobodaThe University of Leeds, Leeds, UK.
Amanda VarnavaImperial College Healthcare NHS Trust, London, UK.
David WrightUniversity of Liverpool / Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
Sanjay PrasadNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0000-0002-5637-0727
Stuart CookMRC Laboratory of Medical Sciences, Imperial College London, London, UK.
Upsala Paz TayalNational Heart and Lung Institute, Imperial College London, London, UK.
Rachel BuchanRoyal Brompton and Harefield Hospitals, Guy's and St. Thomas NHS Foundation Trust, London, UK.ORCID 0000-0003-2490-9289
Roddy WalshCardiovascular and Genomics Research Institute, St George's University of London, London, UK.ORCID 0000-0001-5092-8825
Arthur A M WildeDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.
Benjamin MederDepartment of Medicine III, Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, Heidelberg, Germany.ORCID 0000-0003-0741-2633
Philippe CharronSorbonne Université, Inserm, Unité de recherche sur les maladies cardiovasculaires et métaboliques, ICAN, F-75013 Paris, France.ORCID 0000-0002-1782-1118
Anuj GoelDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.ORCID 0000-0003-2307-4021
Ahmad S AminDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-1600-7907
Patrick T EllinorCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-2067-0533
Krishna G AragamCardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-3223-9131
Rafik TadrosElectrophysiology Service and Adult Congenital Heart Disease Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.ORCID 0000-0002-1472-0258
Yigal M PintoDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-2836-571X
Carolyn Y HoCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7334-7924
Hugh WatkinsDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.ORCID 0000-0002-5287-9016
James S WareNational Heart and Lung Institute & MRC Laboratory of Medical Sciences, Imperial College London, London, UK.ORCID 0000-0002-6110-5880
Connie R BezzinaDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-0633-3514
Sean J JurgensDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-1605-9782
Funding
IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6MGenomics of Cardiac ArrhythmiasR01HL139731 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2018 to 2022
$3.3MUsing Electrocardiogram Genetics to Inform Arrhythmia RiskR01HL157635 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS, MIRSHAHI, TOORAJ · 2022 to 2025
$2.9MPopulation Assessments of Aggregate Genetic Risk for DilatedýCardiomyopathyK08HL153937 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ARAGAM, KRISHNA G · 2021 to 2025
$846kNHLBI NIH HHS K08 HL153937NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL139731NHLBI NIH HHS R01 HL157635
Abstract
Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are heart muscle diseases with largely opposing structural and functional phenotypes. Yet, both may lead to the same devastating outcomes of advanced heart failure and life-threatening arrhythmias. Using genome-wide association data from 9,365 DCM cases, 5,900 HCM cases, and over 1.2 million controls, we show that DCM and HCM are largely inversely associated across multiple genomic levels. Modeling both disorders as opposing genetic entities, in case-case GWAS approaches, we identify 100 loci (17 novel) underlying the cardiomyopathy spectrum. Several loci map to potential therapeutic targets (e.g.,
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.