BrainSeq Phase II: Schizophrenia-Associated Expression Differences Between the Hippocampus and the Dorsolateral Prefrontal Cortex

Background: We previously identified widespread genetic, developmental, and schizophrenia-associated changes in polyadenylated RNAs in the dorsolateral prefrontal cortex (DLPFC), but the landscape of hippocampal (HIPPO) expression using RNA sequencing is less well-explored. Methods: We performed RNA...

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Published in:Human heredity 2018-06, Vol.83 (1), p.42
Main Authors: Collado-Torres, Leonardo, Burke, Emily E, Peterson, Amy, Shin, Joo Heon, Semick, Stephen A, Consortium, BrainSeq, Tao, Ran, Deep-Soboslay, Amy, Hyde, Thomas M, Kleinman, Joel E, Weinberger, Daniel R, Jaffe, Andrew E
Format: Article
Language:English
Subjects:
Age
Brain
Cerebral palsy
Exons
Gene expression
Gene regulation
Hippocampus
Mental disorders
Polyadenylation
Prefrontal cortex
Quantitative trait loci
Ribonucleic acid
RNA
Schizophrenia
Splice junctions
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Summary:Background: We previously identified widespread genetic, developmental, and schizophrenia-associated changes in polyadenylated RNAs in the dorsolateral prefrontal cortex (DLPFC), but the landscape of hippocampal (HIPPO) expression using RNA sequencing is less well-explored. Methods: We performed RNA-seq using RiboZero on 900 tissue samples across 551 individuals (286 with schizophrenia) in DLPFC (N = 453) and HIPPO (N = 447). We quantified expression of multiple feature summarizations of the Gencode v25 reference transcriptome, including genes, exons and splice junctions. Within and across brain regions, we modeled age-related changes in controls using linear splines, integrated genetic data to perform expression quantitative trait loci (eQTL) analyses, and performed differential expression analyses controlling for observed and latent confounders. Results: We identified widespread transcriptional regulation in the DLPFC and the hippocampus over development, with 10,807 genes differentially expressed across age and brain regions that are nominally replicated in BrainSpan. Of these genes, ~55% contain differentially expressed exons and splice junctions that replicated in BrainSpan. We found 48 genes differentially expressed (at FDR
ISSN:0001-5652
1423-0062