基于双样本双向孟德尔随机化的5种自身免疫性疾病与非酒精性脂肪性肝病因果关系分析  

Causal relationship between five autoimmune diseases and NAFLD:a two-sample bidirectional Mendelian randomization study

作　　者：崔娟[1] 陈毅盛 温惠红 曾林琳 闫海震[3] CUI Juan;CHEN Yisheng;WEN Huihong;ZENG Linlin;YAN Haizhen(Department of Traditional Chinese Medicine,The Affiliated Brain Hospital of Guangzhou Medical University,Guangzhou 510370,China;不详)

机构地区：[1]广州医科大学附属脑科医院中医科,广东广州510370 [2]广州市增城区荔城街社区卫生服务中心,广东广州511316 [3]暨南大学附属广州红十字会医院中医老年病科,广东广州510240

出　　处：《山东医药》2025年第3期40-45,共6页Shandong Medical Journal

基　　金：广东省中医药局科研项目(20221302,20242066);广州地区中医药重大科技项目(2025CX018)。

摘　　要：目的基于双样本双向孟德尔随机化分析5种自身免疫性疾病[炎症性肠病(IBD)、银屑病(PsO)、类风湿关节炎(RA)、多发性硬化(MS)和系统性红斑狼疮(SLE)]与非酒精性脂肪性肝病(NAFLD)的因果关系,为免疫性疾病与NAFLD发病风险关联提供遗传学证据支持。方法采用MR Egger回归、加权中位数、随机效应逆方差加权法(IVW)、加权模型和简单模型5种回归模型对5种自身免疫性疾病与NAFLD之间的因果关联进行双样本双向孟德尔随机化分析。结果IVW分析结果显示,IBD与NAFLD存在显著的因果关联(β=0.0466,SE=0.0157,P=0.003),效应值为正相关(OR=1.0477,95%CI:1.0160~1.0805);简单模型结果方向与IVW一致且显著(β=0.1266,SE=0.0541,P=0.0212),进一步支持因果关联的稳健性。IVW未发现RA与NAFLD的显著关联(β=0.0169,SE=0.0187,P=0.3658)。剩余工具变量单核苷酸多态性数量均不足10个,存在统计效力不足或偏倚风险,被排除。结论双样本双向孟德尔随机化分析表明,IBD与NAFLD的发病存在因果关系,IBD可能会增加NAFLD的发病风险。Objective To investigate the causal relationships between five autoimmune diseases such as inflammatory bowel disease(IBD),psoriasis(PsO),rheumatoid arthritis(RA),multiple sclerosis(MS),and systemic lupus erythematosus(SLE)and non-alcoholic fatty liver disease(NAFLD)using a two-sample bidirectional Mendelian randomization(MR)analysis,providing genetic evidence for the association between immune-related disorders and NAFLD risk.Methods A two-sample bidirectional MR analysis was performed to assess causal relationships between the five autoimmune diseases and NAFLD using five regression models:MR Egger regression,weighted median,random-effects inversevariance weighted(IVW)method,weighted mode,and simple mode.Results IVW analysis revealed a significant causal association between IBD and NAFLD(β=0.0466,SE=0.0157,P=0.003),with a positive effect size(OR=1.0477,95%CI:1.0160-1.0805).The simple mode yielded consistent and significant results(β=0.1266,SE=0.0541,P=0.0212),further supporting the robustness of the causal relationship.No significant association was observed between RA and NAFLD using IVW(β=0.0169,SE=0.0187,P=0.3658).Analyses for other autoimmune diseases were excluded due to insufficient instrumental variable SNPs(<10),which posed risks of statistical under-powering or bias.Conclusion The two-sample bidirectional MR analysis indicates a causal relationship between IBD and NAFLD,suggesting that IBD may increase the risk of NAFLD development.

关 键 词：孟德尔随机化 双样本双向孟德尔随机化 非酒精性脂肪性肝病 免疫性疾病 炎症性肠病 共病现象 

分 类 号：R575.5[医药卫生—消化系统]