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Olle Melander

Principal investigator

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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author

  • Sonia Shah
  • Peter Almgren
  • Gunnar Engström
  • Olle Melander
  • Gustav Smith
  • R. Thomas Lumbers

Summary, in English

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 heritability 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. © 2020, The Author(s).

Department/s

  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Epidemiology
  • EpiHealth: Epidemiology for Health
  • WCMM-Wallenberg Centre for Molecular Medicine
  • Cardiovascular Epigenetics
  • Molecular Epidemiology and Cardiology

Publishing year

2020

Language

English

Publication/Series

Nature Communications

Volume

11

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Epigenetics
  • Molecular Epidemiology and Cardiology

ISBN/ISSN/Other

  • ISSN: 2041-1723