Deng Zhen, Wang Kai, Hou Tianshu
Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, Chengdu, China.
Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Brain Behav. 2025 May;15(5):e70513. doi: 10.1002/brb3.70513.
Prior research has indicated a correlation between irritable bowel syndrome (IBS) and suicidal behavior. Nevertheless, it remains uncertain if this correlation implies causation.
We used univariate and multivariate Mendelian randomization. The United Kingdom Biobank provided 53,400 European patients and 433,201 European controls for the IBS GWAS. The outcome variable was developed from a genome-wide association analysis of 26,590 suicide attempt cases and 492,022 controls from the International Suicide Genetics Consortium. BioBank Finland GWAS data (9,771 cases and 402,410 controls) was used for SA validation. Primarily employing inverse variance weighting (IVW), we conducted the analysis to establish causality. MR-Egger and weighted median were used as complementary methods to reinforce the robustness and validity of the results. We used the MRlap method to eliminate the effect of sample overlap. We also used a multivariable MR approach to control for the influence of potential confounders. Using a number of approaches, including the Cochran's Q test, the MR-Egger intercept, and the MR-PRESSO methodology, the study examined pleiotropy and heterogeneity.
We discovered evidence for an elevated risk of suicide attempt with IBS (OR = 1.67, 95% CI = 1.21-2.35, P = 5.52E-07). MRlap analyses similarly support this result. We got the same results with the validation data (OR = 1.19, 95% CI = 1.06-1.34, P = 2.46E-03). The relationships between the different sensitivity analysis approaches were similar, and there was no indication that outliers influenced these correlations. The independent causal impact of IBS on suicide attempts was maintained after controlling for anxiety, depression, and abdominal pain. In reverse MR, we found no causal link between suicide attempt and IBS.
Our MR analysis indicates a causal relationship between IBS and suicide risk. Early detection and intervention in suicidal ideation in IBS patients reduces their suicide risk. More study is needed to understand the mechanisms that link IBS and suicidal behavior, which may alter or broaden therapy for specific individuals.
先前的研究表明肠易激综合征（IBS）与自杀行为之间存在关联。然而，这种关联是否意味着因果关系仍不确定。
我们使用了单变量和多变量孟德尔随机化方法。英国生物银行提供了53400名欧洲IBS患者和433201名欧洲对照用于IBS全基因组关联研究（GWAS）。结局变量来自国际自杀遗传学联盟对26590例自杀未遂病例和492022名对照的全基因组关联分析。芬兰生物银行GWAS数据（9771例病例和402410名对照）用于自杀未遂验证。主要采用逆方差加权（IVW）进行分析以确定因果关系。MR-Egger和加权中位数作为补充方法以加强结果的稳健性和有效性。我们使用MRlap方法消除样本重叠的影响。我们还采用多变量MR方法来控制潜在混杂因素的影响。该研究使用了多种方法，包括 Cochr an's Q检验、MR-Egger截距和MR-PRESSO方法，来检验多效性和异质性。
我们发现了IBS患者自杀未遂风险升高的证据（比值比[OR]=1.67，95%置信区间[CI]=1.21 - 2.35，P = 5.52×10⁻⁷）。MRlap分析同样支持这一结果。验证数据也得到了相同的结果（OR = 1.19，95% CI = 1.06 - 1.34，P = 2.46×10⁻³）。不同敏感性分析方法之间的关系相似，且没有迹象表明异常值影响了这些关联。在控制焦虑、抑郁和腹痛后，IBS对自杀未遂的独立因果影响依然存在。在反向MR分析中，我们未发现自杀未遂与IBS之间存在因果联系。
我们的MR分析表明IBS与自杀风险之间存在因果关系。对IBS患者自杀意念进行早期检测和干预可降低其自杀风险。需要更多研究来了解IBS与自杀行为之间的关联机制，这可能会改变或拓宽针对特定个体的治疗方法。
