Genetic overlap between educational attainment, schizophrenia and autism

Abstract:

Importance The genetic relationship between cognition, autism, and schizophrenia is complex. It is unclear how genes that contribute to cognition also contribute to risk for autism and schizophrenia. Objective To investigate the interaction between genes related to cognition (measured via proxy through educational attainment, which we call ‘edu genes’) and genes/biological pathways that are atypical in autism and schizophrenia. Design Genetic correlation and enrichment analysis were conducted to identify the interaction between edu genes and risk genes and biological pathways for autism or schizophrenia. Results First, edu genes are enriched in a specific developmental co-expression module that is also enriched for high confidence autism risk genes. Second, modules enriched for genes that are dysregulated in autism and schizophrenia are also enriched for edu genes. Finally, genes that overlap between the two above modules and educational attainment are significantly enriched for genes that flank human accelerated regions, suggesting increased positive selection for the overlapping gene sets. Conclusion Our results identify distinct co-expression modules where risk genes for the two psychiatric conditions interact with edu genes. This suggests specific pathways that contribute to both cognitive deficits and cognitive talents, in individuals with schizophrenia or autism. Key Points Question How do genes for educational attainment interact with risk genes for autism and schizophrenia? Findings We show that genes for educational attainment (edu genes) are significantly likely to be mutated in autism and intellectual disability. We further show that edu genes also interact with co-expression modules that are associated with autism or schizophrenia and are enriched for differentially expressed genes in autism or schizophrenia. Finally, we identify that the enrichment between risk genes for autism and schizophrenia and human accelerated regions are driven, in part, by their overlap with edu genes. Meaning Edu genes interact with schizophrenia and autism risk genes in specific pathways, contributing to both cognitive deficits and talents.