Serum Inflammatory Factors Levels and Risk of Myasthenia Gravis: A Bidirectional Mendelian Randomization Study

Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness, where the role of inflammatory processes remains incompletely understood. Bidirectional Mendelian randomization (MR) provides a method to explore potential causal relationships between traits. In this bidirectional MR study, we investigated the relationship between 40 serum inflammatory factors and MG using the two-sample MR approach. The inverse variance weighted (IVW) method was the primary analytical method. Factors with P < 0.05 after false discovery rate (FDR) correction were considered to have a significant causal relationship with MG. Bayesian colocalization and functional mapping were employed to further analyze the instrumental variables. We then used reverse MR to examine potential reverse causality and validated these findings in the UK Biobank-PPP cohort. A phenome-wide association study (PheWAS) was conducted using UK Biobank and FinnGen data to evaluate the potential side effects of targeting these inflammatory factors as therapeutic interventions. Our results indicated that elevated levels of serum interleukin-10 (IL-10) were associated with a decreased risk of MG (P = 9.34E-03, OR [95% CI] = 0.52 [0.33-0.85]). Reverse MR revealed no evidence of reverse causality (P > 0.05), with further validation in the UK Biobank-PPP cohort (P = 3.81E-3, OR [95% CI] = 5.43E-02 [7.54E-03-3.91E-01]). The PheWAS outcomes showed associations of serum IL-10 levels across a broad phenotypic spectrum. Our findings suggest that IL-10 may play a protective role in the pathogenesis of MG. The absence of reverse causality highlights IL-10 as a potential therapeutic target. This study emphasizes the importance of inflammatory factors in autoimmune disorders and supports the utility of MR studies in uncovering novel therapeutic targets.