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

By Elliott Rees, Hugo D. J. Creeth, Hai-Gwo Hwu, Wei J. Chen, Ming T Tsuang, Stephen J Glatt, Romain Rey, Kirov George, James Walters, Peter Holmans, Michael J Owen, Michael C O'Donovan

Posted 02 Sep 2020
bioRxiv DOI: 10.1101/2020.09.02.279265

Genes enriched for rare disruptive coding variants in schizophrenia overlap those in which disruptive mutations are associated with neurodevelopmental disorders (NDDs), particularly autism spectrum disorders and intellectual disability. However, it is unclear whether this implicates the same specific variants, or even variants with the same functional effects on shared risk genes. Here, we show that de novo mutations in schizophrenia are generally of the same functional category as those that confer risk for NDDs, and that the specific de novo mutations in NDDs are enriched in schizophrenia. These findings indicate that, in part, NDDs and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology. We also observe pleiotropic effects for variants known to be pathogenic for several syndromic developmental disorders, suggesting that schizophrenia should be included among the phenotypes associated with these mutations. Collectively, our findings support the hypothesis that at least some forms of schizophrenia lie within a continuum of neurodevelopmental disorders. ### Competing Interest Statement JTRW, MCOD, and MJO are supported by a collaborative research grant from Takeda Pharmaceuticals. Takeda played no part in the conception, design, implementation, or interpretation of this study.

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