Causal Relationship Between Thyroid Function and Multiple Sclerosis: A Bidirectional Mendelian Randomization Study

An association between thyroid function and multiple sclerosis (MS) has been reported in several observational studies, but the causal relationship between them is still unclear. Thus, this study used a bidirectional Mendelian randomization (MR) to investigate the associations between thyroid function and MS. Bidirectional MR was used to explore the causal relationship between thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [FT4], hyperthyroidism, and hypothyroidism) and MS. Genome-wide association study (GWAS) data of thyroid function and MS were obtained from the ThyroidOmics Consortium and the FinnGen Consortium, respectively. Inverse-variance weighted method (IVW) was the primary analysis method to assess causality with Weighted median, MR-Egger regression, weighted mode, and simple mode as auxiliary methods. Sensitivity analyses were performed using heterogeneity tests, horizontal pleiotropy tests and leave-one-out method. There was a positive causal relationship between TSH and MS (IVW: OR = 1.202, 95% CI: 1.040–1.389, P = .013), and no strong evidence was found for an effect of FT4 (IVW: OR = 1.286, 95% CI: 0.990–1.671, P = .059), hypothyroidism (IVW: OR = 1.247, 95% CI: 0.961–1.617, P = .096), and hyperthyroidism (IVW: OR = 0.966, 95% CI: 0.907–1.030, P = .291) on the risk of MS. In the reverse MR results, there was no causal relationship between MS and TSH (IVW: β = −0.009, P = .184), FT4 (IVW: β = −0.011, P = .286), hypothyroidism (IVW: OR = 0.992, 95% CI: 0.944–1.042, P = .745), and hyperthyroidism (IVW: OR = 1.026, 95% CI: 0.943–1.117, P = .549). Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, and Leave-one-out did not observe horizontal pleiotropy and heterogeneity. In conclusion, MR analysis supported a positive causal relationship between TSH and MS.