SynthesisNature genetics2021
Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.
Open access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 9 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed, 9 pooled it
33.9field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
162 citing papers in PubMed, 9 syntheses or guidelines pooled it, 285 citations in OpenAlex.
- A multiancestry polygenic risk score improves stratification in patients with hypertrophic cardiomyopathy.Nature cardiovascular research · 2026Pooled it
- Genome-wide analysis identifies susceptibility loci for heart failure and nonischemic cardiomyopathy subtype in the East Asian populations.PLoS genetics · 2025Pooled it
- Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.Nature genetics · 2025Pooled it
- Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk.Nature genetics · 2025Pooled it
- Meta-Analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy.Circulation · 2024Pooled it
- Research landscape of genetics in dilated cardiomyopathy: insight from a bibliometric analysis.Frontiers in cardiovascular medicine · 2024Pooled it
- A large genome-wide association study of QT interval length utilizing electronic health records.Genetics · 2022Pooled it
- Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure.Nature communications · 2022Pooled it
- Effect of taurine administration on symptoms, severity, or clinical outcome of dilated cardiomyopathy and heart failure in humans: a systematic review.Wellcome open research · 2022Pooled it
- Expanding CIRdb, a comprehensive catalog of whole-exome sequencing data of Canary Islanders.iScience · 2026Article
- Genetic analysis of imaging-derived phenotypes.Nature reviews. Genetics · 2026Review
- Unlocking the Regulatory Genome: Interpreting the Clinical Impact of Noncoding Variants in Genetic Cardiomyopathies.Circulation. Genomic and precision medicine · 2026Review
- Four-dimensional left ventricular motion clustering reveals cardiovascular phenotypes at population scale.Scientific reports · 2026Article
- Early Insights on Mavacamten Usage in Canada: A Retrospective Cohort Study of the Mavacamten Patient Support Program.CJC open · 2026Article
- Beyond sarcomere genetics: proteomic insights into hypertrophic cardiomyopathy.Biophysical reviews · 2026Review
- Single-cell polygenic risk scores dissect cellular and molecular heterogeneity of complex human diseases.Nature biotechnology · 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
- Polygenic Background and Penetrance of Pathogenic Variants in Hypertrophic and Dilated Cardiomyopathies.JAMA cardiology · 2026Article
- Multi-trait and multi-ancestry genetic analysis of comorbid lung diseases and traits improves genetic discovery and polygenic risk prediction.Nature genetics · 2026Article
102 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
70 authors at 20 institutions in 9 countries.
Rafik Tadros *Cardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada. rafik.tadros@umontreal.ca.ORCID http://orcid.org/0000-0002-1472-0258
Catherine Francis *Cardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.
Xiao Xu *MRC London Institute of Medical Sciences, Imperial College London, London, UK.
Alexa M C Vermeer *Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Andrew R HarperDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-5327-0328
Roy HuurmanDepartment of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0001-7405-8668
Ken Kelu BisabuCardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.ORCID http://orcid.org/0000-0003-1453-177X
Roddy WalshDepartment of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-5092-8825
Edgar T HoorntjeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Wouter P Te RijdtDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Rachel J BuchanCardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.ORCID http://orcid.org/0000-0003-2490-9289
Hannah G van VelzenDepartment of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
Marjon A van SlegtenhorstDepartment of Clinical Genetics, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
Jentien M VermeulenDepartment of Psychiatry, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Joost Allard OfferhausDepartment of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Wenjia BaiData Science Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-2943-7698
Antonio de MarvaoMRC London Institute of Medical Sciences, Imperial College London, London, UK.
Najim LahrouchiDepartment of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-1753-452X
Leander BeekmanDepartment of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Jacco C KarperDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Jan H VeldinkDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0001-5572-9657
Elham KayvanpourInstitute for Cardiomyopathies, Heidelberg Heart Center, University of Heidelberg, Heidelberg, Germany.
Antonis PantazisCardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.
A John BaksiCardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.
Nicola WhiffinCardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.ORCID http://orcid.org/0000-0003-1554-6594
Francesco MazzarottoCardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.ORCID http://orcid.org/0000-0002-6159-9980
Geraldine SloaneCardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.
Hideaki SuzukiDepartment of Brain Sciences and UK Dementia Research Institute at Imperial College London, Hammersmith Hospital, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-0410-6940
Deborah Schneider-LuftmanThe Francis Crick Institute, London, UK.
Paul ElliottDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-7511-5684
Pascale RichardService de biochimie métabolique, UF de cardiogénétique et myogénétique moléculaire et cellulaire, APHP, Hôpital Pitié-Salpêtrière, Paris, France.
Flavie AderService de biochimie métabolique, UF de cardiogénétique et myogénétique moléculaire et cellulaire, APHP, Hôpital Pitié-Salpêtrière, Paris, France.ORCID http://orcid.org/0000-0001-7891-3385
Eric VillardINSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Faculté de Médecine, Sorbonne Université, Paris, France.
Peter LichtnerInstitute of Human Genetics, Helmholtz Zentrum Muenchen, Neuherberg, Germany.
Thomas MeitingerInstitute of Human Genetics, Helmholtz Zentrum Muenchen, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-8838-8403
Michael W T TanckDepartment of Clinical Epidemiology, Biostatistics and Bioinformatics, University of Amsterdam, Amsterdam Public Health (APH), Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-9828-4459
J Peter van TintelenDepartment of Clinical Genetics, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-3854-6749
Andrew ThainDepartment of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
David McCartyDepartment of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Robert A HegeleDepartment of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.ORCID http://orcid.org/0000-0003-2861-5325
Jason D RobertsDepartment of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Julie AmyotCardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.
Marie-Pierre DubéMontreal Heart Institute Research Center, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.ORCID http://orcid.org/0000-0001-8442-4393
Julia Cadrin-TourignyCardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.
Geneviève GiraldeauCardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.
Philippe L L'AllierCardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.
Patrick GarceauCardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.
Jean-Claude TardifMontreal Heart Institute Research Center, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.
S Matthijs BoekholdtDepartment of Cardiology, University of Amsterdam, Heartcenter, Amsterdam UMC, Amsterdam, the Netherlands.
R Thomas LumbersInstitute of Health Informatics, University College London, London, UK.ORCID http://orcid.org/0000-0002-9077-4741
Folkert W AsselbergsDepartment of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0002-1692-8669
Paul J R BartonCardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.ORCID http://orcid.org/0000-0002-1165-7767
Stuart A CookNational Heart and Lung Institute, Imperial College London, London, UK.
Sanjay K PrasadCardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.
Declan P O'ReganMRC London Institute of Medical Sciences, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-0691-0270
Jolanda van der VeldenDepartment of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-5224-5788
Karin J H VerweijDepartment of Psychiatry, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-9868-7821
Mario TalajicCardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.
Guillaume LettreMontreal Heart Institute Research Center, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada.
Yigal M PintoDepartment of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-2836-571X
Benjamin MederInstitute for Cardiomyopathies, Heidelberg Heart Center, University of Heidelberg, Heidelberg, Germany.
Philippe CharronEuropean Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARD-HEART).ORCID http://orcid.org/0000-0002-1782-1118
Rudolf A de BoerDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-4775-9140
Imke ChristiaansDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Michelle MichelsDepartment of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
Arthur A M WildeDepartment of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Hugh Watkins *Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-5287-9016
Paul M Matthews *Department of Brain Sciences and UK Dementia Research Institute at Imperial College London, Hammersmith Hospital, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-1619-8328
James S Ware *Cardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK. j.ware@imperial.ac.uk.ORCID http://orcid.org/0000-0002-6110-5880
Connie R Bezzina *Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. c.r.bezzina@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-0633-3514
Montreal Heart Institute · CAAmsterdam Neuroscience · NLNational Health Service · GBUniversity Medical Center Groningen · NLAmsterdam University Medical Centers · NLErasmus MC · NLInserm · FRWestern University · CAHammersmith Hospital · GBMRC London Institute of Medical Sciences · GBUtrecht University · NLCentre for Human Genetics · GBHeidelberg University · DEHelmholtz Zentrum München · DEImperial College London · GBNational University of Singapore · SGRoyal Brompton & Harefield NHS Foundation Trust · GBSt Bartholomew's Hospital · GBThe Francis Crick Institute · GBTUM Klinikum · DE
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 FS/15/81/31817British Heart Foundation NH/17/1/32725British Heart Foundation RE/13/1/30181British Heart Foundation RE/18/4/34215British Heart Foundation RG/18/9/33887British Heart Foundation RG/19/6/34387British Heart Foundation SP/17/11/32885Department of HealthMedical Research Council G0100811Medical Research Council G0300665Medical Research Council G0601966Medical Research Council G0900897Medical Research Council G9409531Medical Research Council G9409634Medical Research Council G9901399Medical Research Council MC_PC_17114Medical Research Council MC_U120085815Medical Research Council MC_UP_1102/19Medical Research Council MC_UP_1102/20Medical Research Council MC_UP_1605/13Medical Research Council MR/K501013/1Medical Research Council MR/M024903/1Medical Research Council MR/N026934/1Medical Research Council MR/S003754/1NHLBI NIH HHS U01 HL117006Wellcome Trust 087183Wellcome Trust 090532/Z/09/ZWellcome Trust 107469Wellcome Trust 107469/Z/15/ZZonMw 91815610
Abstract
The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.
Indexed as
Cardiomyopathy, DilatedCardiomyopathy, HypertrophicCase-Control StudiesGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHeart VentriclesHumansKaplan-Meier EstimateLinkage DisequilibriumPolymorphism, Single NucleotideQuantitative Trait LociVentricular Function, Left
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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.