ArticlemedRxiv : the preprint server for health sciences2023
Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy.
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Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
62 authors at 20 institutions in 6 countries.
Rafik TadrosCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Sean L ZhengNational Heart & Lung Institute, Imperial College London, London, UK.
Christopher GraceRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.
Paloma JordàCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Catherine FrancisNational Heart & Lung Institute, Imperial College London, London, UK.
Sean J JurgensDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Kate L ThomsonRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.
Andrew R HarperRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.
Elizabeth OrmondroydRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.
Dominique M WestRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.
Xiao XuMRC London Institute of Medical Sciences, Imperial College London, London, UK.
Pantazis I TheotokisNational Heart & Lung Institute, Imperial College London, London, UK.
Rachel J BuchanNational Heart & Lung Institute, Imperial College London, London, UK.
Kathryn A McGurkNational Heart & Lung Institute, Imperial College London, London, UK.
Francesco MazzarottoNational Heart & Lung Institute, Imperial College London, London, UK.
Beatrice BoschiGenetics Unit, Careggi University Hospital, Florence, Italy.
Elisabetta PeloGenetics Unit, Careggi University Hospital, Florence, Italy.
Michael LeeNational Heart & Lung Institute, Imperial College London, London, UK.
Michela NosedaNational Heart & Lung Institute, Imperial College London, London, UK.
Amanda VarnavaNational Heart & Lung Institute, Imperial College London, London, UK.
Alexa Mc 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.
Ahmad S AminDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Marjon A van SlegtenhorstDepartment of Clinical Genetics, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Nicole RoslinThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Lisa J StrugDepartments of Statistical Sciences and Computer Science, Data Sciences Institute, University of Toronto, Toronto, ON, Canada.
Erika SalviNeuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Chiara LanzaniGenomics of Renal Diseases and Hypertension Unit, Nephrology Operative Unit, IRCCS San Raffaele Hospital, Milan, Italy.
Antonio de MarvaoNational Heart & Lung Institute, Imperial College London, London, UK.
Hypergenes InterOmics Collaborators
Jason D RobertsSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada.
Maxime Tremblay-GravelCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Genevieve GiraldeauCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Julia Cadrin-TourignyCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Philippe L L'AllierCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Patrick GarceauCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Mario TalajicCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Yigal M PintoDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Harry RakowskiPeter Munk Cardiac Centre, Toronto, ON, Canada.
Antonis PantazisRoyal Brompton & Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
John BaksiNational Heart & Lung Institute, Imperial College London, London, UK.
Brian P HallidayNational Heart & Lung Institute, Imperial College London, London, UK.
Sanjay K PrasadNational Heart & Lung Institute, Imperial College London, London, UK.
Paul Jr BartonNational Heart & Lung Institute, Imperial College London, London, UK.
Declan P O'ReganMRC London Institute of Medical Sciences, Imperial College London, London, UK.
Stuart A CookMRC London Institute of Medical Sciences, Imperial College London, London, UK.
Rudolf A de BoerDepartment of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
Imke ChristiaansDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Michelle MichelsEuropean Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, (ERN GUARD-HEART; https://guardheart.ern-net.eu).
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.
Stefan NeubauerDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, NIHR Oxford Health Biomedical Research Centre, University of Oxford, Oxford, UK.
HCMR Investigators
Paul M MatthewsDepartment of Brain Sciences and UK Dementia Research Institute, Imperial College London, London, UK.
Arthur A WildeDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Jean-Claude TardifCardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.
Iacopo OlivottoDepartment of Experimental and Clinical Medicine, Meyer Children Hospital, University of Florence, Florence, Italy.
Arnon AdlerDivision of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
Anuj GoelRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.
James S WareNational Heart & Lung Institute, Imperial College London, London, UK.
Connie R BezzinaDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Hugh WatkinsRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.
Guy's and St Thomas' NHS Foundation Trust · GBMontreal Heart Institute · CACentre for Human Genetics · GBERN GUARD-Heart · NLBroad Institute · USImperial College London · GBMRC London Institute of Medical Sciences · GBAzienda Ospedaliero-Universitaria Careggi · ITBrigham and Women's Hospital · USErasmus MC · NLNational University of Singapore · SGUniversity Medical Center Groningen · NLWestern University · CAAmsterdam University Medical Centers · NLChurchill Hospital · GBFondazione IRCCS Istituto Neurologico Carlo Besta · ITHospital for Sick Children · CAImperial College Healthcare NHS Trust · GBMeyer Children's Hospital · ITUniversity Health Network · CA
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 BBC/F/21/220106British Heart Foundation CH/1992001/6764British Heart Foundation FS/ICRF/21/26019British Heart Foundation FS/IPBSRF/22/27059British Heart Foundation NH/17/1/32725British Heart Foundation SP/19/2/34462Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_U120085815Medical Research Council MC_UP_1605/13NHLBI NIH HHS U01 HL117006Wellcome Trust
Abstract
Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. We here report results from the largest HCM genome-wide association study (GWAS) and multi-trait analysis (MTAG) including 5,900 HCM cases, 68,359 controls, and 36,083 UK Biobank (UKB) participants with cardiac magnetic resonance (CMR) imaging. We identified a total of 70 loci (50 novel) associated with HCM, and 62 loci (32 novel) associated with relevant left ventricular (LV) structural or functional traits. Amongst the common variant HCM loci, we identify a novel HCM disease gene,
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