Identifying the Genetic Association Between Sjogren's Syndrome and Autoimmune Thyroid Disease: A Bidirectional Two‐Sample Mendelian Randomization Study

BACKGROUND: Although observational studies have suggested a correlation between Sjogren's syndrome (SS) and autoimmune thyroid disease (AITD), a conclusive evidence supporting a causal relationship is still lacking. This study aims to explore the potential causal relationship between SS and AITD. METHODS: Using genome-wide association studies, we performed a bidirectional two-sample Mendelian randomization (MR) analysis. In our analysis, the random-effects inverse variance weighted (IVW) method was predominantly employed, followed by several sensitivity analyses, which include heterogeneity, horizontal pleiotropy, outliers, and "leave-one-out" analyses. RESULTS: In the study of the effect of SS on AITD, SS was associated with an increased risk of Hashimoto's thyroiditis (OR = 1.09, 95%CI 1.02-1.16, p = 0.01). The causal associations were supported by sensitivity analyses. In reverse MR analyses, Hashimoto's thyroiditis (OR = 1.24, 95% CI 1.08-1.42, p < 0.01) and Graves' disease (OR = 1.11, 95% CI 1.03-1.21, p < 0.01) were found to be risk factors for SS. CONCLUSION: Our results support a bidirectional causal relationship between SS and Hashimoto's thyroiditis and a positive correlation of genetically predicted Graves' disease on the risk of SS.