Large-scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy
Montreal Heart Institute · Amsterdam University Medical Centers · +80 more institutions
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…
Citation impact
- FWCI
- 56.06
- Percentile
- 100%
- References
- 67
Authors
127- RTRafik TadrosCorresponding
Montreal Heart Institute, Amsterdam University Medical Centers, Université de Montréal, University of Amsterdam
- SLSean L. Zheng
Guy's and St Thomas' NHS Foundation Trust, Harefield Hospital, MRC London Institute of Medical Sciences, Imperial College London
- CGChristopher Grace
John Radcliffe Hospital, University of Oxford
- PJPaloma Jordà
Montreal Heart Institute, Université de Montréal
- CFCatherine Francis
Guy's and St Thomas' NHS Foundation Trust, Harefield Hospital, Imperial College London
Topics & keywords
- Hypertrophic cardiomyopathy
- Mendelian randomization
- Genome-wide association study
- Biology
- Disease
- Genetics
- Genetic association
- Cardiomyopathy
- Good health and well-being
Funding
- ICIsrael Cancer Research Fund
- WTWellcome TrustAwards: 203141/Z/16/Z, 200990/A/16/Z, 201543/B/16/Z, 200990, 107469, /Z/15/Z, 090532, 203141, 090532/Z/09/Z, 090532/Z/09/, 107469/Z/15/Z
- DZDeutsches Zentrum für Herz-Kreislaufforschung
- MCMaudsley Charity
- ASAlzheimer's Society
- AUAmsterdam University Medical Centers
- CRCancer Research UKAward: RE/13/1/30181
- NINational Institute for Health and Care ResearchAwards: RG/19/6/34387, 203141/Z/16/Z
- BHBritish Heart FoundationAwards: LSHM-CT-2007-037273, RE/18/4/34215, 090532/Z/09/Z, SP/19/2/344612, FS/IPBSRF/22/27059, BBC/F/21/220106, RE/13/1/30181, RG/19/6/34387, FS/ICRF/21/26019, CH/P/23/80008
- DODepartment of Health and Social Care
- ICImperial College LondonAward: RE/18/4/34215
- KCKing's College London
- ECEuropean CommissionAwards: HEALTH-F2-2013-601456, 818715, 601456, LSHM-CT-2007-037273
- FLFondation LeducqAward: 17CVD02
- ZZonMw
- FMFetal Medicine FoundationAward: 495237
- NNNovo Nordisk
- NNNovo Nordisk FondenAward: NNF15CC0018486
- FIFondation Institut de Cardiologie de Montréal
- IDInstitut de Cardiologie de Montréal
- UDUK Dementia Research Institute
- NINational Institutes of HealthAward: U01HL117006-01A1
- IOInstitute of Psychiatry, Psychology and Neuroscience, King’s College London
- ACAmsterdam Cardiovascular Sciences, Amsterdam University Medical Centers
- CICanadian Institutes of Health ResearchAward: 428321
- MRMedical Research CouncilAwards: MC_UP_1605/13, 13/1/30181, 203141/Z/16/Z, RE/18/4/34215
- NHNational Heart, Lung, and Blood InstituteAward: U01HL117006-01A1
- NINational Institute of Mental Health
- NINational Institute on Drug Abuse
- NHNational Human Genome Research Institute
- NONIH Office of the Director
- NCNational Cancer Institute
- NINational Institute of Neurological Disorders and Stroke
- CFCommon Fund