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Exploring the causal association of rheumatoid arthritis with atrial fibrillation: a Mendelian randomization study

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Abstract

Background

It has been proved that rheumatoid arthritis (RA) patients have high incidence of atrial fibrillation (AF). Nevertheless, whether they have causal relevance is uncertain. This study aimed to explore and verify the authenticity of causal relationship between RA and AF using Mendelian randomization (MR).

Methods

The genome-wide association study (GWAS) summary data from Biobank Japan Project (BBJ) (RA, 4199 cases and 208,254 controls) were regarded as exposure data and the GWAS data from European Bio-informatics Institute database (EBI) (AF, 15,979 cases and 102,776 controls) as outcome data. The causal effect was appraised by the inverse variance weighted (IVW) method, MR-Egger regression, and weighted median estimator. MR-robust adjusted profile score (MR-RAPS) method was delivered to examine the robustness of causal relationship and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) method to control horizontal (directional) pleiotropy.

Results

The results indicated that RA increased the risk of AF (IVW, the odds ratio (OR) = 1.060; 95% confidence interval (CI), 1.028 to 1.092; p = 1.411 × 10−4; weighted median, OR = 1.046, 95% CI, 1.002 to 1.093, p = 0.047). The MR analysis also showed this causal effect through all four IVW methods with various statistical algorithms. Both MR-RAPS and MR-PRESSO supported the causality of RA and AF. Also, the MR-PRESSO result indicated the absence of apparent pleiotropy.

Conclusion

There is a causal association between RA and AF. RA patients are genetically more vulnerable to AF. This study may contribute to further exploring early clinical prevention and fundamental mechanism of AF in patients with RA.

Key Points

• We provided some genetic evidence for the causal link between rheumatoid arthritis (RA) and atrial fibrillation (AF) with multiple Mendelian randomization (MR) methods.

• RA patients were genetically more vulnerable to AF.

• This study partly shed light on latent fundamental mechanisms underlying RA-induced AF and inspired future studies on RA-AF relationship.

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Data availability

The datasets applied in this study are readily accessible from the online repositories. This article contains the names of the repositories as well as the accession number.

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Acknowledgements

The authors thank the financial support from Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (Grant Number: 2021KY1072) for checking the R code and the whole process of our entire MR analysis. And we also sincerely appreciate the guidance to our analysis from “Bio-informatics and Clinical Medicine” (WeChat Subscription).

Funding

This study is supported by The Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (Grant No. 2021KY1072).

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Authors and Affiliations

  1. Cardiovascular Department, Ningbo Hangzhou Bay Hospital, Hangzhou Bay New Area, Ningbo, Zhejiang, China

    Jia-cheng Rong, Xu-dong Chen, Na-ke Jin & Jun Hong

  2. Cardiovascular Department, Ningbo Hospital of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jun Hong

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Correspondence to Jun Hong.

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Rong, Jc., Chen, Xd., Jin, Nk. et al. Exploring the causal association of rheumatoid arthritis with atrial fibrillation: a Mendelian randomization study. Clin Rheumatol 43, 29–40 (2024). https://doi.org/10.1007/s10067-023-06804-4

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