Abstract
Background: Previous studies have reported on the relationship between rheumatoid arthritis and ischemic stroke, but it remains unclear whether there is a causal association between rheumatoid arthritis and stroke subtypes.
Methods: In this study, we utilized two-sample Mendelian randomization to investigate the impact of rheumatoid arthritis on stroke and its subtypes. The inverse variance weighted (IVW) method was employed as the primary analysis, while MR-Egger regression, weighted median, simple mode, and weighted mode were used as supplementary analyses to ensure result robustness. We obtained RNA sequencing datasets GSE56649 and GSE58294 from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) associated with both rheumatoid arthritis and cardioembolic stroke. By taking their intersection, we identified common genes for further bioinformatics analyses including gene ontology enrichment analysis, pathway enrichment analysis, and protein-protein interaction (PPI) analysis.
Results: The Mendelian randomization analysis, weighted by inverse variance, demonstrated no significant association between rheumatoid arthritis and ischemic stroke (OR 1.000, 95% CI 0.956-1.042, p=0.921), including its subtypes: small vessel stroke (OR 1.0164, 95% CI 0.922-1.120, p=0.744) and large vessel stroke (OR 0.986, 95% CI 0.891-1.090,p=0.784). However, a positive relationship was observed with cardioembolic stroke (OR 1.094, 95% CI 1.027-1.167,p=0 .006). We identified a total of forty-eight common genes shared between rheumatoid arthritis and cardioembolic stroke and conducted comprehensive enrichment analysis to gain insights into their biological functions and signaling pathways.
Conclusions: The findings of this study provide genetic evidence supporting the association between rheumatoid arthritis and an increased risk of cardioembolic stroke, while no significant relationship was observed with other subtypes of stroke. Through bioinformatics analyses, we identified common gene interaction networks shared by rheumatoid arthritis and cardioembolic stroke, which may offer potential therapeutic targets for clinical applications. However, further laboratory investigations and multicenter studies are warranted to gain a deeper mechanistic understanding in the future.