Zhou Yin, Chen Yuxiao, Wang Pengli, Zhang Kejing, Zhang Yili
Center for Reproductive Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, China.
Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, China.
J Int Med Res. 2025 Aug;53(8):3000605251369855. doi: 10.1177/03000605251369855. Epub 2025 Aug 25.
ObjectiveSchizophrenia is a globally prevalent complex neuropsychiatric disorder that is frequently comorbid with various psychiatric disorders, leading to poor prognoses for affected patients. However, the causal relationships between schizophrenia and these comorbid disorders remain unclear.MethodsWe utilized Mendelian randomization to investigate the causal effects of schizophrenia on eight psychiatric disorders, including alcohol use disorder, anorexia nervosa, anxiety disorders, attention-deficit hyperactivity disorder, autism spectrum disorders, bipolar disorder, depression, and obsessive-compulsive disorder, using data from the Psychiatric Genomics Consortium and other extensive Genome-Wide Association Studies. We employed the inverse variance-weighted method as the primary analysis, complemented by Mendelian randomization-Egger, weighted median, Mendelian randomization-Presso, Steiger filtering, leave-one-out sensitivity analysis, and reverse Mendelian randomization to address potential biases and validate the directionality of the causal relationships.ResultsOur analysis revealed that a genetically predicted one-log unit increase in schizophrenia risk was associated with a 70.7% increase in the odds of bipolar disorder (odds ratio: 1.707, 95% confidence interval: 1.58-1.84). We also found strong evidence regarding a causal relationship of schizophrenia with autism spectrum disorders, showing a 17.4% higher odds (odds ratio: 1.174, 95% confidence interval: 1.11-1.24). Additionally, schizophrenia conferred a 14.5% elevated risk of alcohol use disorder (odds ratio: 1.145, 95% confidence interval: 1.09-1.21), while a statistically significant yet clinically marginal association was observed with depression (odds ratio: 1.004, 95% confidence interval: 1.003-1.006). No causal relationships were detected between schizophrenia and attention-deficit hyperactivity disorder, anorexia nervosa, anxiety disorders, or obsessive-compulsive disorder. Sensitivity analyses reinforced these findings, and reverse Mendelian randomization analyses provided no evidence of reverse causal impacts on schizophrenia from the disorders examined.ConclusionThese findings confirm schizophrenia as a significant genetic risk factor for bipolar disorder, autism spectrum disorders, and alcohol use disorder. Our findings enhance understanding of the interrelationships among psychiatric disorders and offer novel insights into the clinical diagnosis and management of psychiatric comorbidities.
目的
精神分裂症是一种全球普遍存在的复杂神经精神障碍，常与多种精神障碍共病，导致受影响患者预后不良。然而，精神分裂症与这些共病障碍之间的因果关系仍不明确。
方法
我们利用孟德尔随机化方法，使用来自精神疾病基因组学联盟和其他广泛的全基因组关联研究的数据，研究精神分裂症对八种精神障碍的因果效应，这八种精神障碍包括酒精使用障碍、神经性厌食症、焦虑症、注意力缺陷多动障碍、自闭症谱系障碍、双相情感障碍、抑郁症和强迫症。我们采用逆方差加权法作为主要分析方法，并辅以孟德尔随机化-伊格检验、加权中位数法、孟德尔随机化-普雷索检验、施泰格过滤法、留一法敏感性分析和反向孟德尔随机化，以解决潜在偏差并验证因果关系的方向性。
结果
我们的分析显示，遗传预测的精神分裂症风险每增加一个对数单位，双相情感障碍的发病几率就会增加70.7%（优势比：1.707，95%置信区间：1.58 - 1.84）。我们还发现了关于精神分裂症与自闭症谱系障碍存在因果关系的有力证据，其发病几率高出17.4%（优势比：1.174，95%置信区间：1.11 - 1.24）。此外，精神分裂症使酒精使用障碍的风险升高了14.5%（优势比：1.145，95%置信区间：1.09 - 1.21），而与抑郁症存在统计学显著但临床意义不大的关联（优势比：1.004，95%置信区间：1.003 - 1.006）。未发现精神分裂症与注意力缺陷多动障碍、神经性厌食症、焦虑症或强迫症之间存在因果关系。敏感性分析强化了这些发现，反向孟德尔随机化分析未提供所研究障碍对精神分裂症有反向因果影响的证据。
结论
这些发现证实精神分裂症是双相情感障碍、自闭症谱系障碍和酒精使用障碍的重要遗传风险因素。我们的发现增进了对精神障碍之间相互关系的理解，并为精神疾病共病的临床诊断和管理提供了新的见解。
