RT Journal Article
SR Electronic
T1 Selective vulnerability of the brain to mutational classes explain why the same types of genes underlie different neuropsychiatric diseases
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 054460
DO 10.1101/054460
A1 Shahar Shohat
A1 Eyal Ben-David
A1 Sagiv Shifman
YR 2016
UL http://biorxiv.org/content/early/2016/05/20/054460.abstract
AB 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