胆囊切除术与胆管结石的关联:一项孟德尔随机化研究  

Associations of cholecystectomy with calculus of bile duct:a Mendelian randomization study

作　　者：曹佳辉 胡彦建 孙思宇 胡彦华[3] 贺旺 姜博 CAO Jiahui;HU Yanjian;SUN Siyu;Hu Yanhua;He Wang;Jiang Bo(Second Clinical College of Harbin Medical University,Harbin,Heilongjiang 150081,China;Department of Gastroenterology,the First Hospital of Harbin,Harbin,Heilongjiang 150010,China;Department of General Surgery,the Second Affiliated Hospital of Harbin Medical University,Harbin,Heilongjiang 150086,China;Department of Emergency Surgery,the Second Affiliated Hospital of Harbin Medical University,Harbin,Heilongjiang 150086,China)

机构地区：[1]哈尔滨医科大学第二临床医学院,黑龙江哈尔滨150081 [2]哈尔滨市第一医院消化科,黑龙江哈尔滨150010 [3]哈尔滨医科大学附属第二医院普外科,黑龙江哈尔滨150086 [4]哈尔滨医科大学附属第二医院急诊外科,黑龙江哈尔滨150086

出　　处：《肝胆胰外科杂志》2025年第2期93-99,共7页Journal of Hepatopancreatobiliary Surgery

摘　　要：目的基于孟德尔随机化探究胆囊切除术与胆管结石之间的因果关系。方法从公开的全基因组关联研究(GWAS)数据库中获取与胆囊切除术和胆管结石显著相关(P<1×10^(-5))的遗传变异,设定胆囊切除术作为暴露因素,胆管结石作为结局因素。设置r~2<0.01为连锁不平衡参数,遗传距离(kb)>10000为遗传距离,以排除连锁不平衡;LDtrait法手动剔除混杂因素;F统计量评估弱工具变量,取F>10的单核苷酸多态性(SNP)纳入分析,作为暴露因素的工具变量(IVs)。应用逆方差加权(IVW)、倾向性分数匹配(MR-Egger)、加权中位数(weighted median,WM)、简单模式(simple mode)及加权模式法(weighted mode)进行孟德尔随机化分析,评价胆囊切除术与胆管结石之间的因果关系。IVW和MR-Egger的Cochran’s Q检验进行IVs异质性分析,MR-Egger截距进行IVs水平多效性分析,留一法验证分析结果的稳定性。结果筛选分析纳入暴露相关11个IVs。IVW显示胆囊切除术与胆管结石存在因果关系(OR=1.179,95%CI1.123-1.238,P=3.786×10^(-11))。MR-Egger、WM、simple mode、weighted mode分析结果(OR>1)表明胆囊切除术与胆管结石之间存在正相关。IVW和MR-Egger的Cochran Q检验及MR-Egger截距显示IVs无异质性(P>0.05)和水平多效性(P>0.05)。留一法(leave-one-out)显示研究结果稳定。结论胆囊切除术可能增加胆管结石发生风险,尚需临床等效性进一步研究证实。Objective To explore the causal relationship between cholecystectomy and calculus of bile duct by using Mendelian randomization analysis.Methods Genetic variations(P<1×10^(-5))significantly related to cholecystectomy and calculus of bile duct were obtained from the Public Genome-Wide Association Study(GWAS)database.Cholecystectomy was set as the exposure factor,and calculus of bile duct as the outcome factor.The linkage disequilibrium parameters were set as r~2<0.01 and genetic distance was kb>10000 to exclude linkage disequilibrium.LDtrait was used to manually remove confounding factors.SNPs with F statistics>10were included in the analysis and selected as instrumental variables(IVs)for the exposure factor.Mendelian randomization analysis was performed by using inverse variance weighting(IVW),MR-Egger,weighted median,simple mode,and weighted mode analysis methods,to evaluate the causal relationship between cholecystectomy and calculus of bile duct.Cochran's Q test was used for heterogeneity analysis of IVW and MR-Egger,and MREgger intercept for horizontal pleiotropy.The stability of the results was verified by using the leave-one-out method.Results Screening and including 11 instrumental variables(IVs)related to the exposure.The IVW result showed a causal relationship between cholecystectomy and calculus of bile duct(OR=1.179,95%CI 1.123 to 1.238,P=3.786×10^(-11)).The MR analysis results of the MR-Egger,weighted median method,simple mode method,and weighted mode method(OR>1)all supported a positive correlation between cholecystectomy and calculus of bile duct.The Cochran's Q test of IVW and MR-Egger and the MR-Egger intercept term showed no statistical heterogeneity(P<0.05)or horizontal pleiotropy(P<0.05)among IVs highly related to cholecystectomy.The leave-one-out method showed stable analysis results.Conclusion Our study suggests that cholecystectomy may increase the risk of calculus of bile duct,but further clinical equivalence studies are needed to confirm this finding.

关 键 词：胆囊切除术 胆管结石 孟德尔随机化 逆方差加权法 因果关系 

分 类 号：R657.4[医药卫生—外科学] R575.7[医药卫生—临床医学]