Regional Heterogeneity in Gene Expression, Regulation, and Coherence in the Frontal Cortex and Hippocampus across Development and Schizophrenia.

Autor:	Collado-Torres L; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Center for Computational Biology, Johns Hopkins University, Baltimore, MD 21205, USA., Burke EE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA., Peterson A; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA., Shin J; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA., Straub RE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA., Rajpurohit A; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA., Semick SA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA., Ulrich WS; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA., Price AJ; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Valencia C; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA., Tao R; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA., Deep-Soboslay A; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA., Hyde TM; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Kleinman JE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Weinberger DR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Electronic address: drweinberger@libd.org., Jaffe AE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Center for Computational Biology, Johns Hopkins University, Baltimore, MD 21205, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. Electronic address: andrew.jaffe@libd.org.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2019 Jul 17; Vol. 103 (2), pp. 203-216.e8. Date of Electronic Publication: 2019 Jun 04.
DOI:	10.1016/j.neuron.2019.05.013
Abstrakt:	The hippocampus formation, although prominently implicated in schizophrenia pathogenesis, has been overlooked in large-scale genomics efforts in the schizophrenic brain. We performed RNA-seq in hippocampi and dorsolateral prefrontal cortices (DLPFCs) from 551 individuals (286 with schizophrenia). We identified substantial regional differences in gene expression and found widespread developmental differences that were independent of cellular composition. We identified 48 and 245 differentially expressed genes (DEGs) associated with schizophrenia within the hippocampus and DLPFC, with little overlap between the brain regions. 124 of 163 (76.6%) of schizophrenia GWAS risk loci contained eQTLs in any region. Transcriptome-wide association studies in each region identified many novel schizophrenia risk features that were brain region-specific. Last, we identified potential molecular correlates of in vivo evidence of altered prefrontal-hippocampal functional coherence in schizophrenia. These results underscore the complexity and regional heterogeneity of the transcriptional correlates of schizophrenia and offer new insights into potentially causative biology. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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