关键词: GWAS Mendelian randomization causality non-tumor gastrointestinal diseases psychiatric disorders

来  源:   DOI:10.3389/fgene.2024.1392518   PDF(Pubmed)

Abstract:
UNASSIGNED: Previous observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
摘要:
先前的观察性研究揭示了精神疾病(PD)与非肿瘤胃肠道疾病(NTGD)之间的潜在相关性。然而,其因果关系尚不清楚。
我们通过双向双样本孟德尔随机化(MR)研究探索了PD与NTGD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:1.645,95%CI:1.291-2.097,p<0.001)的风险增加有因果关系。同时,基因预测的胃食管反流病有助于增加焦虑障碍的风险(OR:1.425,95%CI:1.295-1.568,p<0.001),溃疡性结肠炎与注意力缺陷/多动障碍风险增加相关(OR:1.042,95%CI:1.008-1.078,p=0.0157)。
我们的研究提供了MR证据来支持紧密的因果关系,并确定了八个PD和八个常见NTGD之间的特定方向。进一步检验因果关系的实验研究,潜在机制,并且需要PD和NTGD的治疗潜力。
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