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

Content Provider	Springer Nature : BioMed Central
Author	Zhang, Zhuxin Li, Le Hu, Zhao Zhou, Likun Zhang, Zhenhao Xiong, Yulong Yao, Yan
Abstract	Background Observational 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. Methods Genetic 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. Results After 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. Conclusions Our 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.
Related Links	https://bmcmedgenomics.biomedcentral.com/counter/pdf/10.1186/s12920-023-01606-8.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	17558794
DOI	10.1186/s12920-023-01606-8
Journal	BMC Medical Genomics
Issue Number	1
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2023-08-14
Access Restriction	Open
Subject Keyword	Human Genetics Microarrays Gene Expression Atrial fibrillation Heart failure Mendelian randomization Causality Genetics
Content Type	Text
Resource Type	Article
Subject	Genetics (clinical) Genetics
Journal Impact Factor	2.1/2023
5-Year Journal Impact Factor	2.5/2023

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