Causal relationship between rheumatoid arthritis and carpal tunnel syndrome: a bidirectional two-sample Mendelian randomization study

Abstract

Abstract Background Although there is considerable evidence of a robust correlation between rheumatoid arthritis (RA) and carpal tunnel syndrome (CTS) in previous research, the causal link between the two remains a topic of controversy. Methods We conducted a two-sample Mendelian randomization (MR) study to explore the causal impact of RA on CTS. We obtained aggregate data from genome-wide association studies (GWAS) of CTS (ebi database and GEO database) and RA (FinnGen database). This study employed five MR analysis methods, with a focus on the inverse variance-weighted (IVW) method. Sensitivity analyses were conducted to ensure the robustness of the results of this study. Additionally, we performed reverse MR analysis. Results We selected 84 and 78 single nucleotide polymorphisms (SNPs) significantly associated with RA from two databases as instrumental variables (IVs), respectively. Our results showed that RA patients have a higher risk of getting CTS regardless of whether the ebi database (IVW, OR = 1.045, 95% CI: 1.016–1.075, P = 0.002) or the GEO database (IVW, OR = 1.001, 95% CI: 1.001–1.002, P = 0.001) is selected for CTS data. However, the MR analysis showed no causal link between CTS and the increased risk of RA (ebi: IVW, OR = 1.084, 95% CI: 0.918–1.279, P = 0.341; GEO: IVW, OR = 1.968, 95% CI: 0.011–360.791, P = 0.799). Conclusion The analysis revealed that RA can increase the risk of CTS, but did not support the causal relationship that CTS can increase the risk of RA.

Keywords

• Rheumatoid arthritis
• Carpal tunnel syndrome
• Mendelian randomization
• Causal relationship
• GWAS