Exploring the bidirectional causal relationship between Autism Spectrum Disorder and Schizophrenia using Mendelian...

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.