Mendelian randomization study of primary biliary cholangitis and autoimmune thyroid dysfunction

Abstract

Abstract: Objective To explore the causal relationship between autoimmune thyroid dysfunction and primary biliary cholangitis (PBC) using two-sample Mendelian randomization (MR) analysis. Methods GWAS summary data were extracted from publicly available genome-wide association studies. In the forward MR, PBC was considered as the exposure, and autoimmune hypothyroidism and hyperthyroidism were considered as outcomes. Single nucleotide polymorphisms (SNPs) closely related to and independent of PBC were selected as instrumental variables (IVs). MR analysis was performed using inverse variance weighted (IVW), MR-Egger regression, weighted mode (WM), and weighted median (WME) methods, with odds ratios (OR) and 95% confidence intervals (CI) to evaluate potential causal associations. Heterogeneity tests, pleiotropy tests, and stepwise exclusion tests were used to assess the stability and reliability of the results. Reverse MR study was also conducted. Results PBC was associated with increased risk of autoimmune hypothyroidism (IVW: OR=1.066, 95%CI:1.043~1.09); and with increased risk of autoimmune hyperthyroidism (IVW: OR=1.166, 95%CI:1.103~1.232). The reverse MR indicated that autoimmune hypothyroidism was associated with increased risk of PBC (IVW: OR=1.184, 95%CI:1.08~1.297), and no promoting effect of autoimmune hyperthyroidism on PBC was found. Conclusion PBC can increase the risk of autoimmune thyroid dysfunction, and autoimmune hypothyroidism is also a risk factor for the development of PBC, but there is no causal association between autoimmune hyperthyroidism and PBC.

Key words: Primary biliary cholangitis, Autoimmune thyroid dysfunction, Mendelian randomization study

DING Hang, LI Xiao-fen, XIONG Yan, LI Yan-yan, CHEN Xiu-ji, WANG Xiao-lin. Mendelian randomization study of primary biliary cholangitis and autoimmune thyroid dysfunction[J]. Chinese Hepatolgy, 2025, 30(11): 1549-1553.

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