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

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


Title: Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
Author: Shah, Sonia
Gudbjartsson, Daniel   orcid.org/0000-0002-5222-9857
Thorsteinsdottir, Unnur   orcid.org/0000-0002-7049-2827
Stefansson, Kari   orcid.org/0000-0003-1676-864X
Date: 2020-01-09
Language: English
Scope: 163
University/Institute: Háskóli Íslands
University of Iceland
School: Verkfræði- og náttúruvísindasvið (HÍ)
School of Engineering and Natural Sciences (UI)
Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Nature Communications;11(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-019-13690-5
Subject: Heart failure; Morbidity; Mortality; Genome-Wide Association Study; Blóðrásarsjúkdómar; Dánartíðni; Erfðarannsóknir
URI: https://hdl.handle.net/20.500.11815/2361

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Citation:

Shah, S., Henry, A., Roselli, C. et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nature Communications 11, 163 (2020). https://doi.org/10.1038/s41467-019-13690-5

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 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.

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