Developmental and genetic regulation of the human cortex transcriptome illuminate schizophrenia pathogenesis.

ABSTRACT: Genome-wide association studies have identified 108 schizophrenia risk loci, but biological mechanisms for individual loci are largely unknown. Using developmental, genetic and illness-based RNA sequencing expression analysis in human brain, we characterized the human brain transcriptome around these loci and found enrichment for developmentally regulated genes with novel examples of shifting isoform usage across pre- and postnatal life. We found widespread expression quantitative trait loci (eQTLs), including many with transcript specificity and previously unannotated sequence that were independently replicated. We leveraged this general eQTL database to show that 48.1% of risk variants for schizophrenia associate with nearby expression. We lastly found 237 genes significantly differentia

SUBMITTER: Jaffe AE 

PROVIDER: S-EPMC6438700 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature