Gustav Smith
Associate professor
Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
Author
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 of 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