克罗恩病与衰弱的双向孟德尔随机化研究  

Association between Crohn's disease and frailty:a bidirectional Mendelian randomization study

作　　者：高亚南 徐涯鑫 朱宇倩 徐军[2] 姚亭 陈亚梅[3] GAO Yanan;XU Yaxin;ZHU Yuqian;XU Jun;YAO Ting;CHEN Yamei(School of Nursing,Anhui University of Chinese Medicine,Hefei,Anhui 230012,China;Tongji University,Shanghai 200092,China;Tenth People's Hospital Affiliated to Tongji University,Shanghai 200072,China)

机构地区：[1]安徽中医药大学护理学院,安徽合肥230012 [2]同济大学,上海200092 [3]同济大学附属第十人民医院,上海200072

出　　处：《预防医学》2023年第11期943-947,共5页CHINA PREVENTIVE MEDICINE JOURNAL

基　　金：国家自然科学基金面上项目(72274135)。

摘　　要：目的采用孟德尔随机化(MR)研究方法分析克罗恩病(CD)与衰弱的因果关系,为制定相应的防治策略提供依据。方法CD的遗传关联数据来自国际炎症性肠病遗传学联盟,包括20883人,收集单核苷酸多态性位点(SNP)12276506个;衰弱的遗传关联数据来自一项包括175226人的Meta分析,收集SNP 7589717个。采用逆方差加权法(IVW),以CD相关的37个SNP为工具变量,衰弱为研究结局进行正向MR分析;以衰弱相关的13个SNP为工具变量,CD为研究结局进行反向MR分析;采用Cochran Q检验评估异质性,采用MR-PRESSO检验和MR-Egger回归法检验水平多效性,采用留一法检验结果的稳健性。结果正向MR分析结果显示,与未患CD者相比,遗传学预测的CD患者的衰弱风险升高(β=0.018,95%CI:0.011~0.026,P<0.05);Cochran Q检验显示不存在异质性(P>0.05),MRPRESSO检验和MR-Egger回归法均未发现工具变量的水平多效性(均P>0.05)。逐个剔除SNP后,MR分析结果稳健。反向MR分析未观察到衰弱与患CD之间的关联(O_(R)=0.740,95%CI:0.206~2.661,P>0.05)。结论遗传学预测的CD与衰弱有关,提示应加强CD患者衰弱相关的筛查和预防。Objective To evaluate the association between Crohn's disease(CD)and frailty using a Mendelian randomiza-tion(MR)approach,so as to provide the evidence for prevention and control strategies.Methods Genetic association data for CD were collected through the International Inflammatory Bowel Disease Genetics Consortium,with 20883 sam-ples and 12276506 single nucleotide polymorphism(SNP),and genetic association data for frailty were collected through a meta-analysis including 175226 samples and 7589717 SNPs.A forward MR analysis was performed using the inverse-variance weighted(IVW)method with 37 CD-associated SNPs as instrumental variables,and frailty as the study outcome,and a reverse MR analysis was performed with 13 frailty-associated SNPs as instrumental variables and CD as the study outcome.The heterogeneity was assessed using the Cochran's Q test,and the horizontal pleiotropy was assessed using the MR-PRESSO global test and MR-Egger regression.In addition,the robustness of the results was ver-ified with the leave-one-out.Results Forward MR analysis results showed that patients with genetically predicted CD had an increased risk of frailty index relative to those without CD(β=0.018,95%CI:0.011-0.026,P<0.05).Cochran's Q test detected no heterogeneity(P>0.05),and neither the MR-PRESSO test nor the MR-Egger regression revealed hori-zontal pleiotropy of instrumental variables(both P>0.05).Leave-one-out analysis showed robustness of the MR analysis results.Reverse MR analysis showed no association between frailty index and the risk of CD(O_(R)=0.740,95%CI:0.206-2.661,P>0.05).Conclusions Genetically predicted CD is associated with an increased risk of frailty.It is suggested that screening and prevention of frailty should be reinforced among CD patients.

关 键 词：克罗恩病 衰弱 孟德尔随机化 因果推断 

分 类 号：R574[医药卫生—消化系统]