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

• DOI: 10.1038/s41467-021-25532-4
• Publication Date: 2021-09-09T10:06:24Z
• Authors: Elliott Rees; Hugo D. J. Creeth; Hai-Gwo Hwu; Wei J. Chen; Ming Tsuang; Stephen J. Glatt; Romain Rey; George Kirov; James T. R. Walters; Peter Holmans; Michael J. Owen; Michael C. O’Donovan
• Keywords: Adult; Male; 0301 basic medicine; Autism Spectrum Disorder; Intellectual and Developmental Disabilities (IDD); Autism; Science; Developmental Disabilities; Biological Psychology; 610; Article; 03 medical and health sciences; Intellectual Disability; Genetics; Psychology; 2.1 Biological and endogenous factors; Humans; Genetic Predisposition to Disease; Aetiology; Child; Genetic Association Studies; Pediatric; Family Health; 0303 health sciences; Q; Neurosciences; Histone-Lysine N-Methyltransferase; Biological Sciences; Serious Mental Illness; Brain Disorders; Pedigree; 3. Good health; Mental Health; Neurodevelopmental Disorders; Mutation; Schizophrenia; Mental health; Female

AbstractPeople 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 × 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.