Key result
Mendelian randomization identified 55 exposure traits, including higher BMI, height, systolic blood pressure, and genetic liability to coronary artery disease, as causal risk factors for AF (P<1e-5).
Why the study?
The prevalence of AF is increasing globally, yet a comprehensive understanding of its causes and consequences remains limited.
What are the causal risk factors for and consequences of atrial fibrillation using a phenome-wide Mendelian randomization approach?
Observational
What are the causal risk factors for and consequences of atrial fibrillation using a phenome-wide Mendelian randomization approach?
p-value: p=<1e-5
Body mass index, height, systolic blood pressure, and coronary artery disease are independent causal risk factors for atrial fibrillation, while proteins like IL-6R may represent therapeutic targets.
MR identifies dozens of potential causal traits for AF; leaves open validation in trials before guiding prevention or therapy.
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. Objectives To assess the causes and consequences of AF via a multi-directional Mendelian randomization (MR) analysis scanning thousands of traits in a hypothesis-free approach. Methods We used publicly available GWAS data centralised and harmonised by the IEU open GWAS database. We assessed the potential causal role of 5048 exposures on risk of AF and the causal role of genetic liability to AF on 10,308 outcomes via two-sample MR analysis. Multivariable MR analysis was further conducted to explore the comparative role 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, 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 prioritising 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 cardioembolic ischemic stroke. Conclusions Body mass index, height, systolic blood pressure and genetic liability to coronary artery diseases are independent causal risk factors for AF. Several proteins including DUSP13, IL-6R and TNFSF12 may represent therapeutic potential for preventing AF.
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Wang et al. (2020) conducted an observational in Atrial fibrillation. 5048 exposure traits was evaluated on Risk of atrial fibrillation (p=<1e-5). Mendelian randomization identified 55 exposure traits, including higher BMI, height, systolic blood pressure, and genetic liability to coronary artery disease, as causal risk factors for AF (P<1e-5).
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