先前的观察性研究揭示了精神疾病（PD）和非肿瘤性胃肠道疾病（NTGD）之间的潜在相关性。然而，它们的因果关系仍不清楚。我们通过双向双样本孟德尔随机化（MR）研究探讨了PD和NTGD之间的因果关系。采用大规模全基因组关联研究（GWAS）汇总统计和双向双样本MR研究来评估PD和NTGD之间的因果关系。使用多重敏感性分析来确定我们结果的稳健性。我们发现重度抑郁症与胃溃疡（OR：1.812，95% CI：1.320-2.487，p < 0.001）和肠易激综合征（OR）风险增加存在因果关系。 ：1.645，95% CI：1.291-2.097，p < 0.001）。同时，基因预测的胃食管反流病会导致焦虑症的风险增加（OR：1.425，95% CI：1.295-1.568，p < 0.001），而溃疡性结肠炎则与注意力缺陷/多动症的风险增加有关（OR： 1.042，95% CI：1.008-1.078，p = 0.0157）。我们的研究提供了 MR 证据来支持密切因果关系并确定 8 个 PD 和 8 个常见 NTGD 之间的具体方向。需要进行实验研究来进一步检验 PD 和 NTGD 的因果关系、潜在机制和治疗潜力。版权所有 © 2024 Liang、Huang、Cheng、Wang、Song、Shu 和 Xie。

Previous observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear.We explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results.We found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320-2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291-2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295-1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008-1.078, p = 0.0157).Our study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.Copyright © 2024 Liang, Huang, Cheng, Wang, Song, Shu and Xie.