Antidepressants and risk of inflammatory bowel disease: A drug-target Mendelian randomization study

IF 4.9 2区医学 Q1 CLINICAL NEUROLOGY

Journal of affective disorders Pub Date : 2025-07-14 DOI:10.1016/j.jad.2025.119919

Ji-Lin Wang , Ye Hu , Zhi-Jun Cao

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引用次数: 0

Abstract

Background

Previous studies have found that antidepressants could reduce the risk of IBD, but the results are controversial. Therefore, a drug-target Mendelian randomization was applied to explore the casual relationship between antidepressants and IBD, aiming to identify new preventive uses for the drugs.

Methods

Target genes corresponding to classic SSRI drugs were obtained from the DrugBank database. eQTL Data was collected from the eQTLGen Consortium database. GWAS data for IBD were retrieved from the FinnGen dataset. The IVW-MR and SMR methods were used for the analysis. Heterogeneity was assessed using the Cochran's Q test, and sensitivity analyses was conducted to verify the reliability of the results.

Results

The IVW-MR analysis indicated a significant correlation between SIGMAR1 and risk of IBD, CD and UC. The OR with 95%CI for IBD was 0.925 (0.885–0.968), for CD was 0.91(0.845–0.979), for UC was 0.942(0.895–0.991). The SMR analysis indicated a significant correlation between SLC29A4 and risk of IBD, CD and UC. The OR with 95%CI was 1.524(1.265–1.784) for IBD, 1.767(1.343–2.19) for CD and 1.613(1.316–1.909) for UC. There were no significant genetic associations between serotonin concentration and IBD. The sensitivity analysis suggested no evidence of heterogeneity or pleiotropy among the reported results.

Conclusion

Activation of SIGMAR1 could reduce the risk of IBD, while activation of SLC29A4 could increase the risk of IBD. Further research is warranted to fully understand the potential role of SSRIs targeted genes in the development and progression of IBD.

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抗抑郁药和炎症性肠病的风险：一项药物靶向孟德尔随机研究。

背景：以前的研究发现抗抑郁药可以降低IBD的风险，但结果存在争议。因此，我们采用药物靶向孟德尔随机化来探索抗抑郁药与IBD之间的因果关系，旨在确定药物的新预防用途。方法：从DrugBank数据库中获取经典SSRI药物对应的靶基因。数据来自eQTLGen Consortium数据库。IBD的GWAS数据来自FinnGen数据集。采用IVW-MR和SMR方法进行分析。采用Cochran’s Q检验评估异质性，并进行敏感性分析以验证结果的可靠性。结果：IVW-MR分析显示SIGMAR1与IBD、CD和UC风险有显著相关性。IBD的OR （95%CI）为0.925 (0.885-0.968)，CD为0.91(0.845-0.979)，UC为0.942（0.895-0.991）。SMR分析显示SLC29A4与IBD、CD和UC风险有显著相关性。IBD的OR （95%CI）为1.524(1.265-1.784)，CD为1.767(1.343-2.19)，UC为1.613（1.316-1.909）。血清素浓度与IBD之间没有明显的遗传关联。敏感性分析显示，在报告的结果中没有异质性或多效性的证据。结论：激活SIGMAR1可降低IBD发病风险，而激活SLC29A4可增加IBD发病风险。为了充分了解SSRIs靶向基因在IBD发生和发展中的潜在作用，需要进一步的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of affective disorders 医学-精神病学

CiteScore

10.90

自引率

6.10%

发文量

1319

审稿时长

9.3 weeks

期刊介绍： The Journal of Affective Disorders publishes papers concerned with affective disorders in the widest sense: depression, mania, mood spectrum, emotions and personality, anxiety and stress. It is interdisciplinary and aims to bring together different approaches for a diverse readership. Top quality papers will be accepted dealing with any aspect of affective disorders, including neuroimaging, cognitive neurosciences, genetics, molecular biology, experimental and clinical neurosciences, pharmacology, neuroimmunoendocrinology, intervention and treatment trials.