Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
Shah, Sonia ; Almgren, Peter LU ; Engström, Gunnar LU ; Melander, Olle LU
; Smith, Gustav
LU
and Lumbers, R. Thomas
(2020)
In Nature Communications
11(1).
- 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... (More)
- 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). (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/53a12482-9dd1-4daa-aa64-79a288cf3ce3
- author
- Shah, Sonia
; Almgren, Peter
LU
; Engström, Gunnar
LU
; Melander, Olle
LU
; Smith, Gustav
LU
and Lumbers, R. Thomas
- author collaboration
- organization
-
- Cardiovascular Research - Hypertension (research group)
- Diabetes - Cardiovascular Disease (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Cardiovascular Research - Epidemiology (research group)
- EpiHealth: Epidemiology for Health
- WCMM-Wallenberg Centre for Molecular Medicine
- Cardiovascular Epigenetics (research group)
- Molecular Epidemiology and Cardiology (research group)
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 11
- issue
- 1
- article number
- 163
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85077697294
- pmid:31919418
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-019-13690-5
- language
- English
- LU publication?
- yes
- id
- 53a12482-9dd1-4daa-aa64-79a288cf3ce3
- date added to LUP
- 2020-01-22 12:33:39
- date last changed
- 2024-01-16 19:23:12
@article{53a12482-9dd1-4daa-aa64-79a288cf3ce3,
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. © 2020, The Author(s).}},
author = {{Shah, Sonia and Almgren, Peter and Engström, Gunnar and Melander, Olle and Smith, Gustav and Lumbers, R. Thomas}},
issn = {{2041-1723}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure}},
url = {{http://dx.doi.org/10.1038/s41467-019-13690-5}},
doi = {{10.1038/s41467-019-13690-5}},
volume = {{11}},
year = {{2020}},
}