Causal link between type 1 diabetes mellitus and juvenile idiopathic arthritis in Europe.

Background: Several observational studies have shown an association between the presence of type 1 diabetes mellitus (T1DM) and the risk of developing juvenile idiopathic arthritis (JIA). The occurrence of comorbidities is a painful for children and their families. Therefore, a bidirectional Mendelian randomization (MR) study was conducted.

Methods: The inverse-variance weighting (IVW), weighted median, MR-Egger and MR-cML methods were used for evaluation. Furthermore, several sensitivity analyses were applied to assess the robustness of the results. LD Score Regression (LDSC) was used as a supplement to MR analysis. After accounting for confounders, The multivariable MR (MVMR) analysis and MVMR-cML methods were conducted to verify the direct effect.

Results: The MR IVW and MR-cML methods revealed a causal association between T1DM status and the risk of developing JIA. However, there was no evidence of a causal relationship between T1DM status and the risk of developing JIAU. The sensitivity analysis suggested that the results were credible. LDSC verified the reliability of MR analysis. MVMR and MVMR-cML methods indicated that the association between T1DM and JIA was independent of confounders.

Conclusion: MR analysis supports a causal association between T1DM status and the risk of developing JIA.

Impact: This study uses bidirectional, LD Score Regression and multivariable Mendelian Randomization to establish a causal link between type 1 diabetes mellitus (T1DM) and juvenile idiopathic arthritis (JIA) in children. Our study addresses gaps in existing research and provides a possible causal relationship between the two diseases for the first time. This analysis provides clinicians with a basis for disease prevention, and effectively reduces the distress caused by comorbidities to children and families. At the same time, it provides some ideas for the study of the related mechanism of T1DM and JIA in children.