原发性胆汁性胆管炎与自身免疫性甲状腺功能障碍的孟德尔随机化研究

肝脏 ›› 2025, Vol. 30 ›› Issue (11): 1549-1553.

原发性胆汁性胆管炎与自身免疫性甲状腺功能障碍的孟德尔随机化研究

丁航, 李小芬, 熊艳, 李艳艳, 陈秀记, 王晓霖

441021 襄阳襄阳市中心医院湖北文理学院附属医院消化二科

收稿日期:2024-08-20 出版日期:2025-11-30 发布日期:2026-02-09
通讯作者: 王晓霖
基金资助:
襄阳市中心医院人才培养工程(2025RCQM-004)

Mendelian randomization study of primary biliary cholangitis and autoimmune thyroid dysfunction

DING Hang, LI Xiao-fen, XIONG Yan, LI Yan-yan, CHEN Xiu-ji, WANG Xiao-lin

Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China

Received:2024-08-20 Online:2025-11-30 Published:2026-02-09
Contact: WANG Xiao-lin

摘要/Abstract

摘要： 目的采用两样本孟德尔随机分析(MR)探讨自身免疫性甲状腺功能障碍与原发性胆汁性胆管炎(PBC)之间的因果关系。方法从公开的全基因组关联研究(GWAS)中提取GWAS汇总数据,正向MR中以PBC作为暴露,以自身免疫性甲状腺功能减退和甲状腺功能亢进作为结局,筛选与PBC密切相关且独立的单核苷酸多态性(SNPs)作为工具变量(IVs),分别运用逆方差加权法(IVW)、MREgger回归、加权众数法(WM)和加权中位数法(WME)进行MR分析,以OR值及95%CI评价潜在的因果关联。采用异质性检验、多效性检验、逐步剔除法检验评估结果的稳定性与可靠性,并进行反向MR研究。结果 PBC与自身免疫性甲状腺功能减退风险增加有关(IVW:OR=1.066,95%CI=1.043~1.09);与自身免疫性甲状腺功能亢进风险增加有关(IVW:OR=1.166,95%CI=1.103~1.232)。反向MR表明,自身免疫性甲状腺功能减退与PBC风险增加有关 (IVW:OR=1.184,95%CI=1.08~1.297),未发现自身免疫性甲状腺功能亢进对PBC存在促进作用。结论 PBC可增加自身免疫性甲状腺功能障碍发生风险,同时,自身免疫性甲状腺功能减退也是促进PBC发生发展的危险因素,但自身免疫性甲状腺功能亢进与PBC之间无因果关联。

关键词: 原发性胆汁性胆管炎, 自身免疫性甲状腺功能障碍, 孟德尔随机化研究

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

丁航, 李小芬, 熊艳, 李艳艳, 陈秀记, 王晓霖. 原发性胆汁性胆管炎与自身免疫性甲状腺功能障碍的孟德尔随机化研究[J]. 肝脏, 2025, 30(11): 1549-1553.

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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