Liang Xiru, Huang Xindi, Cheng Yutong, Wang Ziwei, Song Yahua, Shu Qiuai, Xie Ning
Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Front Genet. 2024 May 9;15:1392518. doi: 10.3389/fgene.2024.1392518. eCollection 2024.
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, < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291-2.097, < 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, < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008-1.078, = 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.
既往观察性研究揭示了精神障碍(PDs)与非肿瘤性胃肠道疾病(NTGDs)之间的潜在关联。然而,它们之间的因果关系仍不明确。
我们通过双向双样本孟德尔随机化(MR)研究探讨了PDs与NTGDs之间的因果关系。使用大规模全基因组关联研究(GWAS)汇总统计数据和双向双样本MR研究来评估PDs与NTGDs之间的因果关系。采用多种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风险增加存在因果关联(比值比:1.812,95%置信区间:1.320 - 2.487,P < 0.001)以及肠易激综合征(比值比:1.645,95%置信区间: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风险增加(比值比:1.425,95%置信区间:1.295 - 1.568,P < 0.001),而溃疡性结肠炎与注意力缺陷多动障碍风险增加有关(比值比:1.042,95%置信区间:1.008 - 1.078,P = 0.0157)。
我们的研究提供了MR证据来支持八种PDs与八种常见NTGDs之间的紧密因果关系,并确定了具体方向。需要进行实验研究以进一步检验PDs与NTGDs之间的因果关系、潜在机制和治疗潜力。