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Somatic mutations arising from the brain have recently emerged as significant contributors to neurodevelopmental disorders, including childhood intractable epilepsy and cortical malformations. However, whether brain somatic mutations are implicated in schizophrenia (SCZ) is not well established.

We performed deep whole exome sequencing (average read depth > 550×) of matched dorsolateral prefrontal cortex and peripheral tissues from 27 patients with SCZ and 31 age-matched control individuals, followed by comprehensive and strict analysis of somatic mutations, including mutagenesis signature, substitution patterns, and involved pathways. In particular, we explored the impact of deleterious mutations in GRIN2B through primary neural culture.

We identified an average of 4.9 and 5.6 somatic mutations per exome per brain in patients with SCZ and control individuals, respectively …