自身免疫性肝病和1型糖尿病之间的遗传联系:一项两样本孟德尔随机化研究  

Genetic Correlation Between Autoimmune Liver Disease and Type 1 Diabetes:A Mendelian Randomization Study

作　　者：邵姝钰 周星 宋自芳 Shao Shuyu;Zhou Xing;Song Zifang(Department of Hepatobiliary Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院肝胆外科,武汉430022

出　　处：《华中科技大学学报(医学版)》2025年第1期22-29,100,共9页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81974040,No.82270412,No.82202000)。

摘　　要：目的采用两样本孟德尔随机化(TSMR)的方法,探究自身免疫性肝病(AILD)与1型糖尿病(T1D)之间潜在的因果关联。方法使用Open GWAS数据库获取不同研究来源的AILD和T1D的全基因关联研究数据(GWAS),以3种AILD为暴露,T1D为结局进行正向孟德尔随机化分析;以T1D为暴露,3种AILD为结局进行逆向孟德尔随机化分析。选择与暴露因素显著相关的单核苷酸多态性(SNP)作为工具变量,采用逆方差加权法(IVW)作为主要研究方法,探讨AILD和T1D之间潜在的双向因果关系。采用异质性检验和水平多效性检验等敏感性分析评价研究结果的稳健性。结果IVW显示,原发性胆汁性胆管炎(PBC)增加T1D发病风险[OR=1.14,95%CI(1.082~1.201),P=9.41×10^(-7)],而原发性硬化性胆管炎(PSC)和自身免疫性肝炎(AIH)与T1D的发病不相关[PSC:OR=1.058,95%CI(0.966~1.159),P=0.223;AIH:OR=0.992,95%CI(0.953~1.033),P=0.706]。T1D增加PBC和PSC发病风险[PBC:OR=1.272,95%CI(1.143~1.416),P=1.024×10^(-5);PSC:OR=1.246,95%CI(1.072~1.448),P=0.004],而与AIH发病不相关[OR=1.032,95%CI(0.931~1.144),P=0.551]。结论本研究表明PBC和T1D互相增加对方的发病风险,并且T1D增加PSC的发病风险,为后续分子机制探讨两者之间的关系提供了新的依据和思路。Objective To investigate the potential causal relationship between autoimmune liver diseases(AILD)and type 1 diabetes(T1D)based on two-sample Mendelian randomization(TSMR)method.Methods Genome-wide association study(GWAS)data were obtained from the Open GWAS database.Forward Mendelian randomization analysis was performed with three types of AILD as exposures and T1D as the outcome,while reverse analysis was conducted with T1D as the exposure and three types of AILD as outcomes.Single nucleotide polymorphism(SNP)that was significantly associated with the exposure was selected as instrumental variable(IV).The inverse variance weighting(IVW)method was employed as the primary analytical approach to explore the bidirectional causal relationships between AILD and T1D.Sensitivity analyses,including heterogeneity tests and horizontal pleiotropy tests,were conducted to ensure the robustness of the results.Results The IVW analysis indicated that primary biliary cholangitis(PBC)increased the risk of T1D(OR=1.14,95%CI:1.082-1.201,P=9.41×10~(-7)),while no significant associations was observed for primary sclerosing cholangitis(PSC)and autoimmune hepatitis(AIH)with T1D(PSC:OR=1.058,95%CI:0.966-1.159,P=0.223;AIH:OR=0.992,95%CI:0.953-1.033,P=0.706).Conversely,T1D was associated with an increased risk of PBC(OR=1.272,95%CI:1.143-1.416,P=1.024×10~(-5))and PSC(OR=1.246,95%CI:1.072-1.448,P=0.004),but not AIH(OR=1.032,95%CI:0.931-1.144,P=0.551).Conclusion This study demonstrates a bidirectional causal relationship between PBC and T1D,and T1D also increases the risk of PSC.These findings provide new insights and directions for future research into the molecular mechanisms underlying these associations.

关 键 词：自身免疫性肝病 1型糖尿病 孟德尔随机化 双向因果关联 

分 类 号：R587.1[医药卫生—内分泌]