昼夜节律紊乱、肠道菌群和炎症性肠病之间的因果关系分析:一项孟德尔随机化研究
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中国博士后科学基金(2022M713841).


Causal relationship among circadian rhythm disruption, gut microbiota, and inflammatory bowel disease: a Mendelian randomization study
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Supported by Postdoctoral Science Foundation of China (2022M713841).

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    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205 527例)和IBD(样本量214 053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18 340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-0.028 740)。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。

    Abstract:

    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=205 527) and IBD (n=214 053) were obtained from IEU OpenGWAS database. Summary statistics of GWAS for the gut microbiota were obtained from the MiBioGen database (n=18 340). 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 -0.028 740). 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.

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  • 收稿日期:2025-05-07
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  • 在线发布日期: 2025-09-22
  • 出版日期: 2025-09-20
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