摘要
目的基于孟德尔随机化(MR)方法探讨昼夜节律紊乱与炎症性肠病(IBD)的因果关系及肠道菌群的中介效应。方法从IEU OpenGWAS数据库获取昼夜节律紊乱(样本量205527例)和IBD(样本量214053例)的全基因组关联研究(GWAS)汇总数据,同时从MiBioGen数据库获取肠道菌群GWAS数据(样本量18340例),通过两样本MR分析评估遗传相关性及因果关系,并采用两步MR分析检验肠道菌群的中介效应。结果昼夜节律紊乱与IBD存在提示性因果关系(OR=1.255,P<0.05),理研菌科(Rikenellaceae,id.967)在两者因果链中发挥中介效应(中介效应为-0.028740)。敏感性分析证实结果未受水平多效性及异质性干扰。结论昼夜节律紊乱与IBD存在遗传相关性,肠道菌群可能在两者之间发挥中介作用。
Objective To investigate the causal relationship between circadian rhythm disruption and inflammatory bowel disease(IBD)and the mediating effect of gut microbiota based on Mendelian randomization(MR).Methods Summary statistics of Genome-wide Association Study(GWAS)for circadian rhythm disruption(n=205527)and IBD(n=214053)were obtained from IEU OpenGWAS database.Summary statistics of GWAS for the gut microbiota were obtained from the MiBioGen database(n=18340).Two-sample MR analysis was used to estimate the genetic correlation and causality between circadian rhythm disruption and IBD,and the mediating effect of the gut microbiota was analyzed by two-step MR analysis.Results There was a suggestive causal relationship between circadian rhythm disruption and IBD(odds ratio=1.255,P<0.05).Rikenellaceae id.967 played a mediating role in the causal chain between them(the mediating effect was-0.028740).Sensitivity analysis confirmed that the results were not interfered by level pleiotropy and heterogeneity.Conclusion There is a genetic correlation between circadian rhythm disruption and IBD,and gut microbiota may play a mediating role between them.
作者
朱虹蓉
冷岳奇
孙嘉岑
谭兴
王伟忠
ZHU Hongrong;LENG Yueqi;SUN Jiacen;TAN Xing;WANG Weizhong(Naval Medical Center,Naval Medical University(Second Military Medical University),Shanghai 200433,China)
出处
《海军军医大学学报》
北大核心
2025年第9期1138-1147,共10页
Academic Journal of Naval Medical University
基金
中国博士后科学基金(2022M713841)。
关键词
昼夜节律紊乱
肠道菌群
炎症性肠病
孟德尔随机化
circadian rhythm disruption
gut microbiota
inflammatory bowel disease
Mendelian randomization
