State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
Eur J Gastroenterol Hepatol. 2024 Nov 1;36(11):1267-1274. doi: 10.1097/MEG.0000000000002825. Epub 2024 Jul 8.
BACKGROUND AND AIMS: Observational studies have shown bidirectional associations between psychological disorders (e.g. depression and anxiety) and functional gastrointestinal disorders. However, whether the relationships are causal is uncertain. Here, we used a bidirectional two-sample Mendelian randomization method to investigate the association between psychological disorders and functional gastrointestinal disorders (FGIDs). METHODS: We obtained genome-wide association study summary statistics for two common psychological disorders: depression (170 756 cases) and anxiety (31 977 cases), as well as for three common FGIDs: functional dyspepsia with 6666 cases, constipation with 26 919 cases, and irritable bowel syndrome (IBS) with 7053 cases. These summary statistics were retrieved from several publicly available genome-wide association study databases. The inverse variance weighted method was used as the main Mendelian randomization method. RESULTS: Inverse variance weighted Mendelian randomization analyses showed statistically significant associations between genetically predicted depression and risk of functional dyspepsia [odds ratio (OR): 1.40, 95% confidence interval (CI): 1.08-1.82], constipation (OR: 1.28, 95% CI: 1.13-1.44), and IBS (OR: 1.51, 95% CI: 1.37-1.67). Genetically predicted anxiety was associated with a higher risk of IBS (OR: 1.13, 95% CI: 1.10-1.17) instead of functional dyspepsia and constipation. In addition, genetically predicted IBS instead of functional dyspepsia and constipation was associated with a higher risk of depression (OR: 1.33, 95% CI: 1.12-1.57) and anxiety (OR: 2.05, 95% CI: 1.05-4.03). CONCLUSION: Depression is a causal risk factor for three common FGIDs. A bidirectional causal relationship between IBS and anxiety or depression was also identified.
背景与目的:观察性研究表明,心理障碍(如抑郁和焦虑)与功能性胃肠疾病之间存在双向关联。然而,这些关系是否具有因果关系尚不确定。在这里,我们使用双向两样本 Mendelian 随机化方法来研究心理障碍与功能性胃肠疾病(FGIDs)之间的关联。
方法:我们获得了两种常见心理障碍(抑郁 170756 例,焦虑 31977 例)和三种常见 FGIDs(功能性消化不良 6666 例,便秘 26919 例,肠易激综合征(IBS)7053 例)的全基因组关联研究汇总统计数据。这些汇总统计数据是从几个公开的全基因组关联研究数据库中检索到的。采用逆方差加权法作为主要 Mendelian 随机化方法。
结果:逆方差加权 Mendelian 随机化分析显示,遗传预测的抑郁与功能性消化不良(OR:1.40,95%置信区间(CI):1.08-1.82)、便秘(OR:1.28,95%CI:1.13-1.44)和 IBS(OR:1.51,95%CI:1.37-1.67)风险之间存在统计学显著关联。遗传预测的焦虑与 IBS(OR:1.13,95%CI:1.10-1.17)风险增加相关,而不是功能性消化不良和便秘。此外,遗传预测的 IBS 而不是功能性消化不良和便秘与抑郁(OR:1.33,95%CI:1.12-1.57)和焦虑(OR:2.05,95%CI:1.05-4.03)的风险增加相关。
结论:抑郁是三种常见 FGIDs 的因果危险因素。还确定了 IBS 与焦虑或抑郁之间的双向因果关系。
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