Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations

People with schizophrenia are enriched for rare coding variants in genes associated with neurodevelopmental disorders, particularly autism spectrum disorders and intellectual disability. However, it is unclear if the same changes to gene function that increase risk to neurodevelopmental disorders also do so for schizophrenia. Using data from 3444 schizophrenia trios and 37,488 neurodevelopmental disorder trios, we show that within shared risk genes, de novo variants in schizophrenia and neurodevelopmental disorders are generally of the same functional category, and that specific de novo variants observed in neurodevelopmental disorders are enriched in schizophrenia (P = 5.0 x 10(-6)). The latter includes variants known to be pathogenic for syndromic disorders, suggesting that schizophrenia be included as a characteristic of those syndromes. Our findings imply that, in part, neurodevelopmental disorders and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology, and support the hypothesis that at least some forms of schizophrenia lie on a continuum of neurodevelopmental disorders. Overlapping genes have been implicated in schizophrenia and neurodevelopmental disorders. Here, the authors overlap de novo variants in the two types of disorders and find variants in these genes with the same functional effect and in some cases the same specific variants.

Automated summary

The study found that within shared risk genes, de novo variants in schizophrenia and neurodevelopmental disorders are generally of the same functional category, and specific de novo variants observed in neurodevelopmental disorders are enriched in schizophrenia. This suggests a shared molecular etiology between neurodevelopmental disorders and schizophrenia, supporting the hypothesis that some forms of schizophrenia may lie on a continuum of neurodevelopmental disorders.