Causal effects between atrial fibrillation and heart failure: evidence from a bidirectional Mendelian randomization study

BMC Medical Genomics

Research

Likun Zhou¹  Zhuxin Zhang¹  Le Li¹  Zhao Hu¹  Yulong Xiong¹  Zhenhao Zhang¹  Yan Yao² 

[1] Fuwai Hospital, National Center for Cardiovascular Diseases, National Key Laboratory, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;Fuwai Hospital, National Center for Cardiovascular Diseases, National Key Laboratory, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;Cardiac Arrhythmia Center, Chinese Academy of Medical Sciences, Fu Wai Hospital, 100037, Beijing, China;

关键词: Atrial fibrillation;    Heart failure;    Mendelian randomization;    Causality;    Genetics;   

DOI  :  10.1186/s12920-023-01606-8

 received in 2023-03-31, accepted in 2023-07-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundObservational studies have suggested a close association between atrial fibrillation (AF) and heart failure (HF), yet the causal effect remains uncertain. In this study, we employed a bidirectional Mendelian randomization analysis to investigate the causal effect of one disease on the other.MethodsGenetic instrumental variables were obtained from large-scale summary-level genome-wide association studies of AF (n = 1,030,836) and HF(n = 1,665,481), respectively. Two-sample Mendelian randomization was conducted to establish causal inferences. Inverse-variance weighted (IVW) was the primary estimate, while additional analyses including MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), MR-Egger, and Weighted median were performed to validate robustness and identify pleiotropy.ResultsAfter accounting for confounding variables, MR analysis suggested a potential causal relationship between AF and HF. An augmented genetic predisposition to atrial fibrillation was associated with an elevated risk of heart failure (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.14–1.22). Likewise, genetically determined heart failure also increased the risk of heart failure (OR = 1.44, 95%CI:1.23–1.68). The robustness of the findings was corroborated through MR sensitivity analyses, and the causal estimates remained consistent when the instrument P-value threshold was tightened.ConclusionsOur bidirectional Mendelian randomization study supports a reciprocal causal relationship between AF and HF. The shared genetic profile of these conditions may provide crucial insights into potential therapeutic targets for the prevention and progression of both disorders. These findings underscore the necessity for further investigation into the underlying molecular mechanisms linking AF and HF, as well as the potential for personalized treatment strategies grounded in genetic profiling.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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