Journal article
Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
Nature communications, Vol.11(1), pp.163-163
12/2020
DOI: 10.1038/s41467-019-13690-5
PMCID: PMC6952380
PMID: 31919418
Abstract
Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed herit-ability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
Details
- Title: Subtitle
- Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- Creators
- Sonia Shah - University of QueenslandAlbert Henry - University College LondonCarolina Roselli - Broad InstituteHonghuang Lin - Boston UniversityGarðar Sveinbjörnsson - AmgenGhazaleh Fatemifar - University College LondonÅsa Hedman - Karolinska InstituteJemma Wilk - PfizerMichael Morley - University of PennsylvaniaMark Chaffin - Broad InstituteAnna Helgadottir - AmgenNiek Verweij - Broad InstituteAbbas Dehghan - Imperial College LondonPeter Almgren - Lund UniversityCharlotte Andersson - Boston UniversityKrishna Aragam - Broad InstituteJohan Ärnlöv - Karolinska InstituteJoshua Backman - Regeneron Genetics Center, 777 Old Saw Mill River Road, TarrytownMary Biggs - University of WashingtonHeather Bloom - Emory UniversityJeffrey Brandimarto - University of Pennsylvania [Philadelphia]Michael Brown - The University of Texas at AustinLeonard Buckbinder - PfizerDavid Carey - Department of Molecular and Functional Genomics, Geisinger, Danville, PADaniel Chasman - Brigham and Women's HospitalXing Chen - Pfizer (Switzerland)Xu Chen - Karolinska InstituteJonathan Chung - Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NYWilliam Chutkow - NovartisJames Cook - University of LiverpoolGraciela Delgado - Heidelberg UniversitySpiros Denaxas - University College of London [London]Alexander Doney - Ninewells Hospital and Medical School [Dundee]Marcus Dörr - Greifswald University HospitalSamuel Dudley - University of MinnesotaMichael E Dunn - RegeneronGunnar Engström - Lund UniversityTonu Esko - University of TartuStephan Felix - Greifswald University HospitalChris Finan - University College LondonIan Ford - University of GlasgowMohsen Ghanbari - Erasmus MCSahar Ghasemi - Greifswald University HospitalVilmantas Giedraitis - Uppsala UniversityFranco Giulianini - Brigham and Women's HospitalJohn Gottdiener - University of Maryland, BaltimoreStefan Gross - Greifswald University HospitalDaníel Guðbjartsson - University of IcelandRebecca Gutmann - Roy J. and Lucille A. Carver College of MedicineChristopher Haggerty - Geisinger Health System [Danville, PA, USA]Pim van der Harst - Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, UtrechtCraig Hyde - PfizerErik Ingelsson - Stanford UniversityJ. Wouter Jukema - Leiden University Medical Center (LUMC)Maryam Kavousi - Erasmus MCKay-Tee Khaw - Department of Public Health and Primary CareMarcus Kleber - Heidelberg UniversityLars Køber - Copenhagen University HospitalAndrea Koekemoer - University of LeicesterClaudia Langenberg - University of CambridgeLars Lind - Uppsala UniversityCecilia Lindgren - University of OxfordBarry London - University of IowaLuca Lotta - University of CambridgeRuth Lovering - University College LondonJian’an Luan - University of Cambridge [UK]Patrik Magnusson - University of Cambridge [UK]Anubha Mahajan - Wellcome Centre for Human GeneticsKenneth Margulies - University of PennsylvaniaWinfried März - Synlab Academy, Synlab Holding Deutschland GmbH, MannheimOlle Melander - Lund UniversityIfy Mordi - University of DundeeThomas Morgan - Vanderbilt UniversityAndrew D. Morris - University of EdinburghAndrew P. Morris - University of EdinburghAlanna C. Morrison - The University of Texas at AustinMichael Nagle - PfizerChristopher Nelson - University of LeicesterAlexander Niessner - Medical University of ViennaTeemu Niiranen - National Institute for Health and Welfare [Helsinki]Michelle O’Donoghue - Birmingham Women's and Children's NHS Foundation TrustAnjali Owens - University of PennsylvaniaColin Palmer - Ninewells Hospital and Medical School [Dundee]Helen Parry - University of DundeeMarkus Perola - National Institutes of HealthEliana Portilla-Fernandez - Erasmus MCBruce Psaty - University of WashingtonKenneth Rice - University of WashingtonPaul Ridker - Harvard UniversitySimon Romaine - University Hospitals LeicesterJerome Rotter - The Lundquist InstitutePerttu Salo - National Institutes of HealthVeikko Salomaa - National Institutes of HealthJessica van Setten - Utrecht UniversityAlaa Shalaby - University of PittsburghDiane Smelser - Geisinger Health System [Danville, PA, USA]Nicholas Smith - Kaiser PermanenteSteen Stender - Copenhagen University HospitalDavid Stott - University of GlasgowRegeneron Genetics Center
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.11(1), pp.163-163
- DOI
- 10.1038/s41467-019-13690-5
- PMID
- 31919418
- PMCID
- PMC6952380
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 12/2020
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984297498902771
Metrics
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