Table1_A comprehensive Mendelian randomization study highlights the relationship between psychiatric disorders and non-tumor gastrointestinal diseases.XLSX

ObjectivePrevious observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear.
MethodsWe 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.
ResultsWe 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).
ConclusionOur 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.

研究目的：既往观察性研究显示精神障碍（psychiatric disorders, PDs）与非肿瘤性胃肠道疾病（non-tumor gastrointestinal diseases, NTGDs）存在潜在关联，但二者的因果关系仍不明确。
研究方法：本研究通过双向两样本孟德尔随机化（Mendelian randomization, MR）分析，探讨精神障碍与非肿瘤性胃肠道疾病之间的因果关系。研究采用大规模全基因组关联研究（genome-wide association study, GWAS）汇总统计数据结合双向两样本孟德尔随机化方法，评估二者的因果关联，并通过多项敏感性分析验证研究结果的稳健性。
研究结果：本研究发现，重度抑郁症与胃溃疡（比值比（odds ratio, OR）: 1.812, 95%置信区间（confidence interval, CI）: 1.320–2.487, p < 0.001）及肠易激综合征（OR: 1.645, 95% CI: 1.291–2.097, p < 0.001）的发病风险升高存在因果关联。同时，经遗传预测的胃食管反流病可增加焦虑障碍的发病风险（OR: 1.425, 95% CI: 1.295–1.568, p < 0.001），而溃疡性结肠炎与注意缺陷/多动障碍的发病风险升高相关（OR: 1.042, 95% CI: 1.008–1.078, p = 0.0157）。
研究结论：本研究提供了孟德尔随机化证据，证实8种精神障碍与8种常见非肿瘤性胃肠道疾病之间存在明确的因果关联，并明确了具体的作用方向。未来需开展实验研究，进一步验证二者的因果关系、潜在机制及治疗潜力。