Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder.

ABSTRACT: Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We int

SUBMITTER: Gandal MJ 

PROVIDER: S-EPMC6443102 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature