Jiang Ziqing, Zhou Yiying, Zhou Yingxin, Yang Dongmei, Li Jingjun, Li Yongchun, Fan Qin, Lin Jintao
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Medicine (Baltimore). 2025 Apr 11;104(15):e42119. doi: 10.1097/MD.0000000000042119.
Autism Spectrum Disorder (ASD), characterized mainly by stereotyped behaviors and social impairments, affects about one in 100 children worldwide. Schizophrenia (SCZ), a chronic mental illness, affects 1% of the global population. The pathogenesis and specific treatment strategies for ASD and SCZ remain unclear. Previous research has suggested similarities in SCZ and ASD etiology and symptoms. However, no definitive correlation has been confirmed. Therefore, we conducted a Mendelian randomization study to assess the relationship between SCZ and ASD, providing new insights into their etiology and treatment. We used the two-sample Mendelian randomization (TSMR) approach to investigate the bidirectional causal association between SCZ and ASD, employing summary-level genome-wide association studies (GWAS) data. ASD summary data from the IEU GWAS database and SCZ summary data from the Psychiatric Genomics Consortium (PGC) were used as exposure and outcome variables, respectively. Statistical analysis was performed using the TwoSampleMR package in R version 4.3.2, with sensitivity analysis conducted to verify the result's reliability. Based on the results of the MR analysis, we retrieved and analyzed the relevant genetic information from the GWAS Catalog. TSMR analysis revealed higher ASD risk in SCZ (IVW: OR: 1.19, 95% CI: 1.12-1.26, P < .001). Bidirectional MR analysis confirmed a causal relationship between ASD and SCZ (IVW: scz2018clozuk (Clozapine UK), OR: 1.12, 95% CI: 1.04-1.21, P = .003; scz2019asi, OR: 1.14, 95% CI: 1.05-1.23, P = .002). Our study demonstrated a bidirectional relationship between SCZ and ASD in the European population, suggesting that each may induce the onset of the other.
自闭症谱系障碍（ASD）主要以刻板行为和社交障碍为特征，全球约每100名儿童中就有1人受其影响。精神分裂症（SCZ）是一种慢性精神疾病，影响着全球1%的人口。ASD和SCZ的发病机制及具体治疗策略仍不明确。先前的研究表明SCZ和ASD在病因和症状方面存在相似之处。然而，尚未证实存在明确的相关性。因此，我们进行了一项孟德尔随机化研究，以评估SCZ和ASD之间的关系，为它们的病因和治疗提供新的见解。我们采用双样本孟德尔随机化（TSMR）方法，利用汇总水平的全基因组关联研究（GWAS）数据，研究SCZ和ASD之间的双向因果关联。分别将来自IEU GWAS数据库的ASD汇总数据和来自精神基因组学联盟（PGC）的SCZ汇总数据用作暴露变量和结果变量。使用R 4.3.2版本中的TwoSampleMR软件包进行统计分析，并进行敏感性分析以验证结果的可靠性。基于孟德尔随机化分析结果，我们从GWAS目录中检索并分析了相关遗传信息。TSMR分析显示，SCZ患者患ASD的风险更高（逆方差加权法：比值比：1.19，95%置信区间：1.12 - 1.26，P < 0.001）。双向孟德尔随机化分析证实了ASD和SCZ之间存在因果关系（逆方差加权法：scz2018clozuk（英国氯氮平），比值比：1.12，95%置信区间：1.04 - 1.21，P = 0.003；scz2019asi，比值比：1.14，95%置信区间：1.05 - 1.23，P = 0.002）。我们的研究表明，在欧洲人群中SCZ和ASD之间存在双向关系，这表明两者可能相互诱发对方发病。
