Objective Two-sample Mendelian randomization (TSMR) method was used to explore the potential causal association between Hashimoto thyroiditis (HT) and primary biliary cholangitis (PBC).

Methods The genome-wide association study (GWAS) data of HT and PBC from different research sources were obtained through the IEU OpenGWAS project database. Taking HT as the exposure factor and PBC as the outcome, single nucleotide polymorphisms (SNPs) significantly associated with exposure factor were selected as the instrumental variables (IVs), and inverse-variance weighed (IVW) was used as the main analysis method to explore the potential causal relationship between HT and PBC. Additionally, multiple sensitivity analyses such as heterogeneity test and horizontal multiple effect test were employed to evaluate the robustness and consistency of the findings.

Results The results of random-effects inverse-variance weighted (rIVW) method indicated a significant association between HT and the development of PBC (OR＝1.853, 95%CI 1.241-2.768, P＝0.003), and the results of the other four MR methods based on different assumptions were similar to the rIVW. Sensitivity analysis showed that the results were not affected by horizontal pleiotropy, and the robustness of the results was confirmed by leaving-one test. Reverse MR analysis, due to the presence of horizontal pleiotropy and failure to meet the criteria of the MR Egger test, could not establish a reverse causality of PBC on HT.

Conclusions HT may be a risk factor for the occurrence of PBC, and there is no evidence to support reverse causality. This may potentially offer novel insights into the pathogenesis of both diseases, thereby providing avenues for further research, as well as clues for the prevention and treatment of these two conditions.