自身免疫性肝病与妊娠结局的孟德尔随机化研究

摘要/Abstract

摘要： 目的探讨自身免疫性肝病(AILDs)与妊娠结局的因果关联。方法本研究采用了孟德尔随机化(MR)方法。从大规模全基因组关联研究数据库中分别提取并筛选出与原发性胆汁性胆管炎(PBC)、原发性硬化性胆管炎(PSC)和自身免疫性肝炎(AIH)密切相关的单核苷酸多态性作为工具变量。应用逆方差加权法(IVW)作为MR研究的主要分析方法,MR-Egger回归、加权中位法、简单模式法和权重模式法作为补充分析方法来评估因果效应。进行多项敏感性分析以评估研究结果的可靠性。结果本研究结果显示,PBC与早产(IVW OR:1.0298; 95% CI: 1.0088 ~ 1.0511; P=0.0051)和后代出生体重(IVW beta: -0.0166; 95% CI: -0.0225 ~ -0.0107; P=3.14×10^-8)之间存在因果关联。PSC与异位妊娠(IVW OR: 1.0558, 95% CI: 1.0179 ~ 1.0951; P=0.0036)和自发性流产(IVW OR: 1.0004; 95% CI: 1.0001 ~ 1.0006; P=0.0181)呈正相关。而AIH与产后抑郁(IVW OR:1.0436, 95% CI: 1.0045 ~ 1.0843; P=0.0285) 的风险增加相关。敏感性分析提示不存在异质性和水平多效性。结论本研究为AILDs与妊娠结局之间的因果关系提供了新证据。

关键词: 自身免疫性肝病, 妊娠结局, 孟德尔随机化

Abstract: Objective To investigate the causal links between autoimmune liver diseases (AILDs) and pregnancy outcomes. Methods Mendelian randomization analysis was utilized in this study. From large-scale genome-wide association study (GWAS) databases, single nucleotide polymorphisms highly related to primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) were extracted and selected to act as instrumental variables. Inverse variance weighted (IVW) served as the primary analytical method, supplemented by MR-Egger, weighted median, simple model, and weighted model to evaluate causal effects. Moreover, multiple sensitivity analyses were performed to ensure the robustness of the results. Results This MR study found causal effects of PBC on both preterm birth (IVW OR:1.0298; 95% CI: 1.0088 to 1.0511; P=0.0051) and offspring birth weight (IVW beta: -0.0166; 95% CI: -0.0225 to -0.0107; P=3.14×10^-8). PSC was positively associated with ectopic pregnancy (IVW OR: 1.0558, 95% CI: 1.0179 to 1.0951; P=0.0036) and spontaneous abortion (IVW OR: 1.0004; 95% CI: 1.0001 to 1.0006; P=0.0181), while AIH was linked to an increased risk of postpartum depression (OR=1.0436; 95% CI 1.0045 to 1.0843; P=0.0285). Conclusion This study offers novel evidence supporting causal relationships between AILDs and pregnancy outcomes.

Key words: Autoimmune liver diseases, Pregnancy outcomes, Mendelian randomization

袁艺, 熊梓辰, 邓雪婷, 缪林. 自身免疫性肝病与妊娠结局的孟德尔随机化研究[J]. 肝脏, 2025, 30(5): 713-721.

YUAN Yi, XIONG Zi-chen, DENG Xue-ting, MIAO Lin. Autoimmune liver diseases and pregnancy outcomes: a Mendelian randomization study[J]. Chinese Hepatolgy, 2025, 30(5): 713-721.

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