Genetic causality between multiple sclerosis and atopic dermatitis: A univariable and multivariable Mendelian randomization study

Objective We sought to estimate the genetic causal association between multiple sclerosis (MS) and atopic dermatitis (AD) and identify potential mediating factors. Methods We used univariable Mendelian randomization (UVMR) with inverse variance weighting (IVW) as the primary study method to estimate the causal effect of MS on AD, supplemented by weighted median and MR Egger validation analyses. Furthermore, we conducted a reverse MR analysis. Sensitivity analyses were performed using Cochran's Q test, MR-Egger intercept test, leave-one-out, and funnel plot analysis to evaluate the robustness of the MR findings. Additionally, multivariable MR (MVMR) was employed to estimate the direct causal effect of MS on the risk of AD. Results UVMR analysis demonstrated a genetic predisposition associated with the risk of MS and AD with an odds ratio of 1.10 (95% Confidence Interval: 1.05 to 1.15, P  = 1.87 × 10^ ⁻⁵ ). Consistent results were observed after adjusting for potential confounders, including Body Mass Index (BMI), telomere length, vitamin deficiencies, and smoking-related factors in MVMR analyses. However, following adjustment for C-reactive protein, serum levels of 25-hydroxyvitamin D, and smoking status as confounders, MS was no longer identified as a risk factor for AD. Conclusions The findings indicate that while there may be a genetic link between MS and AD, the causal pathway is complex and influenced by multiple biological and environmental factors. Further research is needed to elucidate these interactions and their implications for disease prevention and treatment strategies.