Damaging coding variants within kainate receptor channel genes are enriched in individuals with schizophrenia, autism and intellectual disabilities.

ABSTRACT: Schizophrenia (Scz), autism spectrum disorder (ASD) and intellectual disability are common complex neurodevelopmental disorders. Kainate receptors (KARs) are ionotropic glutamate ion channels involved in synaptic plasticity which are modulated by auxiliary NETO proteins. Using UK10K exome sequencing data, we interrogated the coding regions of KAR and NETO genes in individuals with Scz, ASD or intellectual disability and population controls; performed follow-up genetic replication studies; and, conducted in silico and in vitro functional studies. We found an excess of Loss-of-Function and missense variants in individuals with Scz compared with control individuals (p = 1.8 × 10^-10), and identified a significant burden of functional variants for Scz (p < 1.6 × 10^-11) and

SUBMITTER: Koromina M 

PROVIDER: S-EPMC6915710 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature