Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China; Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Clinical Medicine, Guangzhou Medical University, Guangzhou, China.
J Psychiatr Res. 2024 Apr;172:244-253. doi: 10.1016/j.jpsychires.2024.02.030. Epub 2024 Feb 13.
The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.
胃食管反流病（GERD）与各种神经退行性和精神疾病之间的共病已被广泛报道。然而，GERD 与这些疾病之间的遗传相关性、因果关系和潜在机制在很大程度上仍不清楚。在这里，我们进行了双向孟德尔随机化（MR）分析，以确定 GERD 与 6 种神经退行性和精神疾病之间的因果关系。进行了敏感性分析和多变量 MR 分析，以检验我们研究结果的稳健性。连锁不平衡得分回归用于评估这些疾病之间受遗传影响的遗传相关性。应用多种生物信息学工具，结合两种机器学习算法，进一步探讨了这些疾病的潜在机制。我们发现，遗传预测的 GERD 显著增加了阿尔茨海默病、重度抑郁症和焦虑症的风险。GERD 和失眠之间可能存在双向关系。GERD 与 AD、ALS、焦虑症、失眠和抑郁症具有不同程度的遗传相关性。生物信息学分析揭示了 GERD 和 6 种神经退行性和精神疾病之间的共享基因和共同途径。我们的研究结果表明这些疾病之间的遗传结构具有复杂性，并阐明了它们的因果关系，突出了 GERD 的治疗方法可能成为预防和管理神经退行性和精神疾病的潜在策略。
