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. 2024 May 16:15:1389549.
doi: 10.3389/fimmu.2024.1389549. eCollection 2024.

Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study

Chang Liu  1   2 , Jiangnan Ye  1 , Shixiu He  3 , Zhijun Ma  1 , Fang Luo  1 , Jintao Miao  2 , Huinan Li  2 , Puhua Cao  4 , Jun Zhu  1   2
Affiliations

Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study

Chang Liu et al. Front Immunol. .

Abstract

Background: Several previous studies have reported an association between rheumatoid arthritis (RA) and epilepsy, but the causal relationship is unclear. The aim of this study was to assess the connection between RA and epilepsy in a European population using Mendelian randomization (MR).

Methods: Genome-wide association study summary data on RA and epilepsy from European populations were included. Univariate MR (UVMR) and multivariate MR were used to investigate the causal relationship between the two conditions. Three analysis methods were applied: inverse variance weight (IVW), MR-Egger, and weighted median, with IVW being the primary method. Cochran Q statistics, MR-PRESSO, MR-Egger intercept, leave-one-out test, and MR-Steiger test were combined for the sensitivity analysis.

Results: UVMR showed a positive association between RA and epilepsy risk (OR=1.038, 95% CI=1.007-1.038, p=0.017) that was supported by sensitivity analysis. Further MVMR after harmonizing the three covariates of hypertension, alcohol consumption, and smoking, confirmed the causal relationship between RA and epilepsy (OR=1.049, 95% CI=1.011-1.087, p=0.010).

Conclusion: This study demonstrated that RA is associated with an increased risk of epilepsy. It has emphasized that the monitoring of epilepsy risk in patients diagnosed with RA should be strengthened in clinical practice, and further studies are needed in the future to explore the potential mechanism of action connecting the two conditions.

Keywords: Mendelian randomization; autoimmunity; central nervous system; epilepsy; rheumatoid arthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of MR study design.
Figure 2
Figure 2
Scatterplot of MR estimates for RA associated with epilepsy.
Figure 3
Figure 3
Funnel plots of MR estimates for RA associated with epilepsy.
Figure 4
Figure 4
Leave-one-out test plots of MR estimates for RA associated with epilepsy.
Figure 5
Figure 5
The forest plot depicts the findings of the MVMR analyses on the causal effects of RA on epilepsy. OR, odds ratio; CI, confidence interval; P-value, p value of the causal estimate.
See this image and copyright information in PMC

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