Department of Endoscopy, The First Hospital of Jilin University, Changchun, Jilin, China.
Mol Genet Genomic Med. 2024 Mar;12(3):e2413. doi: 10.1002/mgg3.2413.
The association between major depressive disorder (MDD) and irritable bowel syndrome (IBS) has been found in observational research; however, the causative relationship between MDD and IBS remains uncertain. Using the two-sample Mendelian randomization (MR) approach, we attempted to examine the causal effect of MDD on IBS.
Independent genetic variants for MDD identified by Howard et al. based on a genome-wide meta-analysis were selected for this study. Gene-Outcome associations for IBS were gathered from UK Biobank and FinnGen databases. The MR analysis included inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-PRESSO sensitivity analyses.
FinnGen database subjected to inverse variance weighted (IVW) analysis revealed that MDD may be a risk factor for the development of IBS (OR = 1.356, 95% CI: 1.125-1.632, p = 0.0013). The same finding was reached in UK Biobank for IVW (OR = 1.011, 95% CI: 1.006-1.015, p = 3.18 × 10 ), MR-Egger progression (OR = 1.030, 95% CI: 1.008-1.051, p = 0.007), and weighted median (OR = 1.011, 95% CI: 1.005-1.016, p = 0.0001).
Our findings supported a causal relationship between MDD and IBS, which may have implications for the clinical management of IBS in individuals with MDD.
在观察性研究中发现,重度抑郁症(MDD)与肠易激综合征(IBS)之间存在关联;然而,MDD 与 IBS 之间的因果关系仍不确定。本研究采用两样本孟德尔随机化(MR)方法,旨在检验 MDD 对 IBS 的因果效应。
Howard 等人基于全基因组荟萃分析确定的用于本研究的 MDD 独立遗传变异。IBS 的基因-结局关联数据来自 UK Biobank 和 FinnGen 数据库。MR 分析包括逆方差加权(IVW)、MR-Egger 回归、加权中位数、加权众数和 MR-PRESSO 敏感性分析。
FinnGen 数据库经 IVW 分析显示,MDD 可能是 IBS 发展的危险因素(OR=1.356,95%CI:1.125-1.632,p=0.0013)。UK Biobank 数据库也得出了类似的 IVW 结果(OR=1.011,95%CI:1.006-1.015,p=3.18×10)、MR-Egger 检验(OR=1.030,95%CI:1.008-1.051,p=0.007)和加权中位数(OR=1.011,95%CI:1.005-1.016,p=0.0001)。
本研究结果支持 MDD 与 IBS 之间存在因果关系,这可能对 MDD 患者的 IBS 临床管理具有重要意义。