Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Regional heterogeneity in gene expression, regulation and coherence in hippocampus and dorsolateral prefrontal cortex across development and in schizophrenia

View ORCID ProfileL Collado-Torres, EE Burke, A Peterson, JH Shin, RE Straub, A Rajpurohit, View ORCID ProfileSA Semick, WS Ulrich, Consortium BrainSeq, C Valencia, R Tao, A Deep-Soboslay, TM Hyde, JE Kleinman, DR Weinberger, View ORCID ProfileAE Jaffe
doi: https://doi.org/10.1101/426213
L Collado-Torres
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
2Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for L Collado-Torres
EE Burke
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A Peterson
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
JH Shin
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
RE Straub
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A Rajpurohit
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SA Semick
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for SA Semick
WS Ulrich
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Consortium BrainSeq
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C Valencia
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R Tao
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A Deep-Soboslay
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TM Hyde
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
4Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
5Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
JE Kleinman
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
5Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DR Weinberger
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
4Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
5Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
6McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
7Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: drweinberger@libd.org andrew.jaffe@libd.org
AE Jaffe
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
2Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA
4Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
6McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
8Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
9Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for AE Jaffe
  • For correspondence: drweinberger@libd.org andrew.jaffe@libd.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Recent large-scale genomics efforts have better characterized the molecular correlates of schizophrenia in postmortem human neocortex, but not hippocampus which is a brain region prominently implicated in its pathogenesis. Here in the second phase of the BrainSeq Consortium (Phase II), we have generated RiboZero RNA-seq data for 900 samples across both the dorsolateral prefrontal cortex (DLPFC) and the hippocampus (HIPPO) for 551 individuals (286 affected by schizophrenia disorder: SCZD). We identify substantial regional differences in gene expression, in both pre- and post-natal life, and find widespread differences in how genes are regulated across development. By extending quality surrogate variable analysis (qSVA) to multiple brain regions, we identified 48 and 245 differentially expressed genes (DEG) by SCZD diagnosis (FDR<5%) in HIPPO and DLPFC, respectively, with surprisingly minimal overlap in DEG between the two brain regions. We further identified 205,618 brain region-dependent eQTLs (FDR<1%) and found that 124 GWAS risk loci contain eQTLs in at least one of the regions. We also identify 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 suggest future schizophrenia therapeutics may need to target molecular pathologies localized to specific brain regions.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted September 26, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Regional heterogeneity in gene expression, regulation and coherence in hippocampus and dorsolateral prefrontal cortex across development and in schizophrenia
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Regional heterogeneity in gene expression, regulation and coherence in hippocampus and dorsolateral prefrontal cortex across development and in schizophrenia
L Collado-Torres, EE Burke, A Peterson, JH Shin, RE Straub, A Rajpurohit, SA Semick, WS Ulrich, Consortium BrainSeq, C Valencia, R Tao, A Deep-Soboslay, TM Hyde, JE Kleinman, DR Weinberger, AE Jaffe
bioRxiv 426213; doi: https://doi.org/10.1101/426213
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Regional heterogeneity in gene expression, regulation and coherence in hippocampus and dorsolateral prefrontal cortex across development and in schizophrenia
L Collado-Torres, EE Burke, A Peterson, JH Shin, RE Straub, A Rajpurohit, SA Semick, WS Ulrich, Consortium BrainSeq, C Valencia, R Tao, A Deep-Soboslay, TM Hyde, JE Kleinman, DR Weinberger, AE Jaffe
bioRxiv 426213; doi: https://doi.org/10.1101/426213

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8765)
  • Bioengineering (6480)
  • Bioinformatics (23345)
  • Biophysics (11751)
  • Cancer Biology (9149)
  • Cell Biology (13255)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15087)
  • Genetics (10402)
  • Genomics (14009)
  • Immunology (9122)
  • Microbiology (22046)
  • Molecular Biology (8780)
  • Neuroscience (47372)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2208)
  • Systems Biology (6016)
  • Zoology (1250)