Causal Relationships between Common Autoimmune Disease and Carpal Tunnel Syndrome: Study of Univariable and Multivariable Mendelian Randomization.

Abstract

Abstract Purpose Whether Autoimmune diseases (AIDs) are a risk factor for carpal tunnel syndrome (CTS) is questionable and has been reported in observational studies, but the quality of the evidence is low and inconclusive. Our study intends to assess the causal association between common AIDs and CTS through univariable and multivariable mendelian randomization (MR). Methods we mainly utilized univariable MR analysis through IVW. Weighted median, MR-Egger analysis to assess the association of AIDs and CTS. Then, we extended the limits of univariable MR analysis through multivariable mendelian randomization in IVW, Egger method, Lasso and median method. The mediating effect was calculated by mediating MR. Finally, the MR-PRESSO, Cochran's Q test and F-values are calculated to assess the levels of pleiotropy, heterogeneity, and intensity of selected IVs and exposures through mediated MR. Results Univariable MR results showed a positive correlation from RA, GD, T1D to ILD with an increased relative risk. While, adjusting by other two AIDs through multivariable mendelian randomization, only T1D is robustly correlated with CTS. T1D can also produce effects on CTS through RA, GD as mediators. Furthermore, the outcome of MR-Egger intercept did not provide evidence of horizontal pleiotropy. The F-value results were all greater than 10, indicating that the selected IV and exposure intensities were appropriate. Conclusion Based on the results of univariable mendelian randomization analysis, the study found genetic evidence supporting a positive causal relationship from RA, T1D, GD to CTS, but only T1D maintained consistent results after multivariable MR analysis. In addition, 24.3% and 25.1% of the effects of T1D on CTS were mediated by RA and GD, respectively. Therefore, appropriate intervention of T1D can reduce the incidence of CTS. Treatment of T1D should be considered a primary preventive measure for CTS.