Based on existing observational study results, there is a potential association between the risk of developing multiple sclerosis (MS) and autoimmune thyroid disease (AITD), but the findings are still controversial.

This study aims to use the Mendelian randomization (MR) method to assess the causal relationship between MS and AITD.

In this study, data from genome-wide association studies (GWAS) were used to summarize MS (case number=47 429, control number=68 374), autoimmune hyperthyroidism (case number=1 991, control number=305 175), Graves' disease (case number=3 176, control number=409 005), and autoimmune thyroiditis (case number=539, control number=349 717). A bidirectional MR analysis was used to evaluate the potential causal relationship. The MR analysis mainly used the random effects inverse variance weighted method, supplemented by new MR analysis methods such as MR-Egger regression, weighted median method, weighted model, corrected maximum likelihood method-pleiotropy analysis, robust corrected profile score, and debiased inverse variance weighted method. In addition, sensitivity tests, such as Cochran Q test, MR-Presso, MR-Egger regression, and leave-one-out test, were used to ensure the robustness of the results.

The MR results showed a causal association between MS and autoimmune thyroiditis (OR=1.144, 95%CI=1.029-1.272, P=0.013, PFDR=0.039), indicating that genetically predicted MS may increase the risk of autoimmune thyroiditis by 14%. The results were consistent after correction for false discovery rate, and there was no heterogeneity (Q-pval=0.356) and horizontal pleiotropy (P=0.359). The leave-one-out analysis did not show any abnormal SNP values, and the Outlier-corrected analysis results showed no outliers detected. The reverse MR analysis showed no significant causal association between AITD and MS.

The risk of autoimmune thyroiditis in MS patients is increased, but there is no obvious association with the risk of developing autoimmune hyperthyroidism and Graves' disease.