失眠与肠易激综合征之间的孟德尔随机化研究

A Mendelian Randomization Study between Insomnia and Irritable Bowel Syndrome

摘要: 目的：由于异质性和混杂因素，失眠与肠易激综合征之间的因果关系尚未明确，即使在随机对照试验(RCT)中也是如此。本研究旨在通过孟德尔随机化(MR)探究失眠与肠易激综合征之间的因果关系，并为未来RCT的优化提供补充信息。方法：从GAWS数据库中提取了失眠和肠易激综合征的GWAS数据，进行两样本孟德尔随机化研究，采用逆方差加权法(Inverse Variance Weighted, IVW)、Egger回归法(MR-Egger)、中位数加权法(Weighted Median)等评估失眠与肠易激综合征之间的因果关联，同时采用异质性检验(Heterogeneity Test)、水平多效性检验(Horizontal Pleiotropy Test)、Leave-One-Out Sensitivity Test进行敏感性分析，评估MR分析的可靠性和稳定性。结果：共纳入25个与失眠密切相关的SNP，遗传预测的失眠与肠易激综合征的风险有关(OR: 3.44, 95% CI: 1.59~7.41; P = 0.001)。结论：遗传预测的失眠与肠易激综合征的风险有关，失眠是肠易激综合征的危险因素。

Abstract: Purpose: The causal relationship between insomnia and irritable bowel syndrome has not been clearly established due to heterogeneity and confounding factors, even after being randomized. The same is true in controlled trials (RCTs). The aim of this study was to explore the causal relationship between insomnia and irritable bowel syndrome by Mendelian Randomization (MR) and to provide additional information for future RCT optimization. Methods: GWAS data on insomnia and irritable bowel syndrome were extracted from the GAWS database, and a two-sample Mendelian Randomization study was conducted to assess the relationship between insomnia by using the inverse variance Weighted (IVW) method, Egger Regression (MR-Egger), and Weighted Median method. The causal association between insomnia and Irritable Bowel Syndrome (IBS) was assessed, and the reliability and stability of the MR analysis were also evaluated by using the Heterogeneity Test, Horizontal Pleiotropy Test, and Leave-One-Out Sensitivity Test for sensitivity analysis. Results: A total of 25 SNPs strongly associated with insomnia were included, and genetically predicted insomnia was associated with the risk of irritable bowel syndrome (OR: 3.44, 95% CI: 1.59~7.41; P = 0.001). Conclusion: Genetically predicted insomnia is associated with the risk of irritable bowel syndrome, and insomnia is a risk factor for irritable bowel syndrome.