Selective vulnerability of the brain to mutational classes explain why the same types of genes underlie different neuropsychiatric diseases

BioRxiv : the Preprint Server for Biology
Shahar ShohatSagiv Shifman


Genetic susceptibility to Intellectual disability (ID), autism spectrum disorder (ASD) and schizophrenia (SCZ) often arises from mutations in the same genes, suggesting that they share common mechanisms. We studied genes with 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 function 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.

Related Concepts

Cerebral Cortex
Corpus Striatum Structure
Disease Susceptibility
Gene Expression
Gene Mutation

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.


Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research.