Abstract
Genetic susceptibility to Intellectual disability (ID), autism spectrumdisorder (ASD) and schizophrenia (SCZ) often arises from mutations in the same genes, suggesting that they share common mechanisms. We studied geneswith de novo mutations in the three disorders and genes implicated by a SCZ genome-wide association study (GWAS). Using biological annotations and brain gene expression, we show that the type of mutation explains enrichment patterns. Across disorders, genes with loss of functio mutations and genes with missense mutations were enriched with different pathways, shared with genes highly intolerant to mutations. Expression patterns in the brain account for differences between disorders. Compared to ID, ASD genes are preferentially expressed also in fetal cerebellum and striatum; genes associated with SCZ were most significantly enriched in adolescent cortex. Our study suggests that convergence across neuropsychiatric disorders stems from pathways that are vulnerable to genetic variations, but the spatiotemporal activity of genes contributes to specific phenotypes