Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
Date
2020Journal
Nature CommunicationsPublisher
Nature ResearchType
Article
Metadata
Show full item recordAbstract
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 UniversityIdentifier 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/10713/11694ae974a485f413a2113503eed53cd6c53
10.1038/s41467-019-13690-5
Scopus Count
Collections
Related articles
- Meta-Analysis of 26 638 Individuals Identifies Two Genetic Loci Associated With Left Ventricular Ejection Fraction.
- Authors: Choquet H, Thai KK, Jiang C, Ranatunga DK, Hoffmann TJ, Go AS, Lindsay AC, Ehm MG, Waterworth DM, Risch N, Schaefer C
- Issue date: 2020 Aug
- Mendelian randomization of circulating proteome identifies actionable targets in heart failure.
- Authors: Moncla LM, Mathieu S, Sylla MS, Bossé Y, Thériault S, Arsenault BJ, Mathieu P
- Issue date: 2022 Aug 13
- Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.
- Authors: van der Harst P, Verweij N
- Issue date: 2018 Feb 2
- Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study.
- Authors: Xia J, Guo C, Liu K, Xie Y, Cao H, Peng W, Sun Y, Liu X, Li B, Zhang L
- Issue date: 2021 Jun 1
- Genetic variants associated with risk of atrial fibrillation regulate expression of PITX2, CAV1, MYOZ1, C9orf3 and FANCC.
- Authors: Martin RI, Babaei MS, Choy MK, Owens WA, Chico TJ, Keenan D, Yonan N, Koref MS, Keavney BD
- Issue date: 2015 Aug