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

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    Author
    Shah, S.
    Gottdiener, J.S.
    Regeneron Genetics Center
    Date
    2020
    Journal
    Nature Communications
    Publisher
    Nature Research
    Type
    Article
    
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    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. Copyright 2020, The Author(s).
    Sponsors
    Bayer; AstraZeneca; Johnson and Johnson; Janssen Biotech; Abbott Laboratories; Eisai; Merck; GlaxoSmithKline; Bayer; Yale University
    Keyword
    cardiovascular genetics
    Genome-Wide Association Study
    Heart Failure
    Epidemiology
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077697294&doi=10.1038%2fs41467-019-13690-5&partnerID=40&md5=c57248ec833d909fe3e998238d284f21; http://hdl.handle.net/10713/11694
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-019-13690-5
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