肠易激综合征与骨质疏松症的因果关系分析  

Analysis of causal relationship between irritable bowel syndrome and osteoporosis

作　　者：张智升 邓欣怡 艾自胜[2] 刘粤 杨铁毅[3] ZHANG Zhisheng;DENG Xinyi;AI Zisheng;LIU Yue;YANG Tieyi(School of Gongli Hospital Medical Technology,University of Shanghai for Science and Technology,Shanghai 200093,China;不详)

机构地区：[1]上海理工大学公利医院医疗技术学院,上海200093 [2]同济大学医学院,上海200082 [3]上海市浦东新区公利医院骨科,上海200135

出　　处：《山东医药》2025年第4期93-97,103,共6页Shandong Medical Journal

基　　金：上海市卫生健康委员会科研项目(202340144);上海市浦东新区卫生健康委员会卫生科技项目(PW2024A-13);上海市浦东新区卫生健康委员会临床特色学科项目(PWYts2021-05)。

摘　　要：目的分析肠易激综合征(IBS)与骨质疏松症(OP)的因果关系,从遗传学角度为OP的预防提供参考。方法从全基因组关联研究公开数据库中获取IBS和OP的数据集,采用双向孟德尔随机化(MR)分析方法,分别从正反方向探讨IBS与OP的因果关系。正向MR分析以与IBS相关的单核苷酸多态性(SNP)为工具变量,IBS为暴露因素,OP为结局变量;反向MR分析以与OP相关的SNP为工具变量,OP为暴露因素,IBS为结局变量。以逆方差加权分析法(IVW)作为主要MR分析方法,以加权中位数(WM)、MR-Egger回归法、简单模型和加权模型进行辅助分析,评价IBS与OP的因果关系。采用MR-Egger截距法评估工具变量的水平多效性,Cochrane's Q检验评估工具变量的异质性,漏斗图对称性评估潜在发表偏倚,留一法评估单个SNP对因果关系影响的敏感性。结果正向MR分析中共纳入56个SNP作为工具变量;IVW分析结果显示,IBS与OP存在正向因果关系(OR=1.0028,95%CI:1.0007~1.0048,P=0.0073);WM、简单模式法和加权模式法分析结果均与IVW分析得到的结果方向一致;MR-Egger截距法、Cochrane's Q检验、漏斗图、留一法分析均显示分析结果可靠。反向MR分析中共纳入50个SNP作为工具变量;IVW分析结果显示,IBS与OP不存在反向因果关系(OR=2.8385,95%CI:0.5464~14.7470,P=0.2146);MR-Egger回归法、WM、简单模式法和加权模式法分析均发现IBS与OP不存在反向因果关系(P均>0.05);MR-Egger截距法、漏斗图、留一法分析均显示分析结果可靠,Cochrane's Q检验提示所纳入的SNP之间存在异质性,但不影响因果推断的稳健性。结论IBS与OP发病风险增加有显著因果关系,而OP与IBS发病风险增加不存在显著因果关系。Objective To analyse the causal relationship between irritable bowel syndrome(IBS)and osteoporosis(OP)and to provide a genetic perspective for the prevention of OP.Methods The datasets of IBS and OP were obtained from the genome-wide association studies(GWAS)public database,and two-way Mendelian randomisation(MR)analyses were used to explore the causal relationship between IBS and OP from forward and reverse directions,respectively.For-ward MR analysis used single-nucleotide polymorphisms(SNPs)associated with IBS as instrumental variables,IBS as ex-posure factor and OP as outcome variable;the reverse MR analysis used SNPs associated with OP as instrumental vari-ables,OP as exposure factor and IBS as outcome variable.Inverse variance weighted(IVW)analysis was used as the pri-mary MR analysis method,supplemented by weighted median(WM),MR-Egger regression,simple and weighted models to assess the causal relationship between IBS and OP.The MR-Egger intercept method was employed to assess the horizon-tal multiplicity of instrumental variables,Cochrane's Q test was utilized to assess the heterogeneity of the instrumental vari-ables,funnel plot symmetry was used to observe the potential publication bias,and leave-one-out method was used to as-sess the sensitivity of individual SNP to causal effects.Results Fifty-six SNPs were included as instrumental variables in the forward MR analysis;IVW analysis showed a positive causal association between IBS and OP(OR=1.0028,95%CI:1.0007-1.0048,P=0.0073);WM,simple mode method and weighted mode method analyses were in the same direc-tion as the IVW analysis results;MR-Egger intercept method,Cochrane's Q test,funnel plot and leave-one-out analysis all showed reliable results.A total of 50 SNPs were included as instrumental variables in the reverse MR analyses;IVW analyses showed that there was no reverse causality between IBS and OP(OR=2.8385,95%CI:0.5464-14.7470,P=0.2146);MR-Egger regression method,WM,simple model method,and weighted model method analyses all found no reverse causal

关 键 词：肠易激综合征 骨质疏松症 因果关系 孟德尔随机化 

分 类 号：R574.4[医药卫生—消化系统]