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.

根据现有的观察性研究结果，多发性硬化症（MS）与自身免疫性甲状腺疾病（AITD）的发病风险之间存在潜在关联，但结果仍存在争议。

旨在采用孟德尔随机化（MR）方法评估MS与AITD之间的因果关系。

本研究使用全基因组关联研究（GWAS）汇总MS（病例组=47 429，对照组=68 374）、自身免疫性甲状腺功能亢进症（病例组=1 991，对照组=305 175）、Graves病（病例组=3 176，对照组=409 005）和自身免疫性甲状腺炎（病例组=539，对照组=349 717）的数据，使用双向MR分析来评估可能的潜在因果关系，MR分析主要采用随机效应逆方差加权法，辅以MR-Egger回归法、加权中位数法、加权模型以及校正最大似然法-多效性分析、稳健校正轮廓评分和去偏反方差加权法等新的MR分析方法。此外，还使用了敏感性检验来确保结果的稳健性，如Cochran Q检验、MR-Presso、MR-Egger回归和留一法检验。

MR结果显示MS与自身免疫性甲状腺炎存在因果关联（OR=1.144，95%CI=1.029~1.272，P=0.013，PFDR=0.039），遗传预测的MS可能会使自身免疫性甲状腺炎的风险增加14%，经错误发现率校正后的结果一致，且结果无异质性（Q-pval=0.356）和水平多效性（P=0.359），留一分析没有显示任何异常单核苷酸多态性值，且Outlier-corrected分析结果显示未检测到离群值。反向MR分析显示AITD与MS之间不存在因果关联。

MS患者发生自身免疫性甲状腺炎的风险增高，但与自身免疫性甲状腺功能亢进症和Graves病的发病风险无关联。