Journal article
Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 2.2MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-019-13690-5
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 11
- Issue:
- 1
- Article number:
- 163
- Publication date:
- 2020-01-09
- Acceptance date:
- 2019-11-18
- DOI:
- EISSN:
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2041-1723
- ISSN:
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2041-1723
- Pmid:
-
31919418
- Language:
-
English
- Keywords:
- Pubs id:
-
1081909
- Local pid:
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pubs:1081909
- Deposit date:
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2020-04-06
Terms of use
- Copyright holder:
- Shah et al.
- Copyright date:
- 2020
- Rights statement:
- © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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