Journal article
A phenome-wide bidirectional Mendelian randomization analysis of atrial fibrillation
- Abstract:
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Background: The prevalence of atrial fibrillation (AF) is increasing with an aging worldwide population, yet a comprehensive understanding of its causes and consequences remains limited. We aim to assess the causes and consequences of AF via a bidirectional Mendelian randomization (MR) analysis.
Methods: We used publicly available genome-wide association study (GWAS) summary data, centralized and harmonized by an open GWAS database. We assessed the genetically predicted effects of 5048 exposures on risk of AF, and the genetically predicted effects of genetic liability to AF, on 10 308 outcomes via two-sample MR analysis. Multivariable MR analysis was further conducted to explore the comparative roles of identified risk factors.
Results: MR analysis suggested that 55 out of 5048 exposure traits, including four proteins, play a causal role in AF (P <1e-5 allowing for multiple comparisons). Multivariable analysis suggested that higher body mass index, height and systolic blood pressure as well as genetic liability to coronary artery diseases independently cause AF. Three out of the four proteins (DUSP13, TNFSF12 and IL6R) had a drug prioritizing score for atrial fibrillation of 0.26, 0.38 and 0.88, respectively (values closer to 1 indicating stronger evidence of the protein as a potential drug target). Genetic liability to AF was linked to a higher risk of cardio-embolic ischaemic stroke.
Conclusions: Our results suggest body mass index, height, systolic blood pressure and genetic liability to coronary artery disease are independent causal risk factors for AF. Several proteins, including DUSP13, IL-6R and TNFSF12, may have therapeutic potential for AF.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.3MB, Terms of use)
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- Publisher copy:
- 10.1093/ije/dyac041
Authors
- Publisher:
- Oxford University Press
- Journal:
- International Journal of Epidemiology More from this journal
- Volume:
- 51
- Issue:
- 4
- Pages:
- 1153-1166
- Publication date:
- 2022-03-15
- Acceptance date:
- 2022-03-01
- DOI:
- EISSN:
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1464-3685
- ISSN:
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0300-5771
- Pmid:
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35292824
- Language:
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English
- Keywords:
- Pubs id:
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1246342
- Local pid:
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pubs:1246342
- Deposit date:
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2023-01-24
Terms of use
- Copyright holder:
- Wang et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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