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

Identification of Brain Expression Quantitative Trait Loci Associated with Schizophrenia and Affective Disorders in Normal Brain Tissue

View ORCID ProfileOneil G. Bhalala, Artika P. Nath, UK Brain Expression Consortium, View ORCID ProfileMichael Inouye, View ORCID ProfileChristopher R. Sibley
doi: https://doi.org/10.1101/068007
Oneil G. Bhalala
1Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Oneil G. Bhalala
  • For correspondence: obhalala@student.unimelb.edu.au c.sibley@imperial.ac.uk
Artika P. Nath
1Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia
2Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Inouye
1Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia
3Department of Pathology, The University of Melbourne, Parkville 3010, Victoria, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael Inouye
Christopher R. Sibley
1Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia
4Department of Molecular Neuroscience, University College London Institute of Neurology, Russell Square House, Russell Square, London WC1B 5EH, United Kingdom
5Department of Medicine, Division of Brain Sciences, Imperial College London, Burlington Danes, DuCane Road, LondonW12 0NN, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Christopher R. Sibley
  • For correspondence: obhalala@student.unimelb.edu.au c.sibley@imperial.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Schizophrenia and the affective disorders, here comprising bipolar disorder and major depressive disorder, are psychiatric illnesses that lead to significant morbidity and mortality worldwide. Whilst understanding of their pathobiology remains limited, large case-control studies have recently identified single nucleotide polymorphisms (SNPs) associated with these disorders. However, discerning the functional effects of these SNPs has been difficult as the associated causal genes are unknown. Here we evaluated whether schizophrenia and affective disorder associated-SNPs are correlated with gene expression within human brain tissue. Specifically, to identify expression quantitative trait loci (eQTLs), we leveraged disorder-associated SNPs identified from six Psychiatric Genomics Consortium and CONVERGE Consortium studies with gene expression levels in post-mortem, neurologically-normal tissue from two independent human brain tissue expression datasets (UK Brain Expression Consortium (UKBEC) and Genotype-Tissue Expression (GTEx)). We identified 6 188 and 16 720 cis-acting SNPs exceeding genome-wide significance (p<5x10−8) in the UKBEC and GTEx datasets, respectively. 1 288 cis-eQTLs were significant in a metaanalysis leveraging overlapping brain regions and were associated with expression of 15 genes, including three non-coding RNAs. One cis-eQTL, rs 16969968, results in a functionally disruptive missense mutation in CHRNA5, a schizophrenia-implicated gene. Meta-analysis identified 297 trans-eQTLs associated with 24 genes that were significant in a region-specific manner. Importantly, comparing across tissues, we find that blood eQTLs largely do not capture brain cis-eQTLs. This study identifies putatively causal genes whose expression in region-specific brain tissue may contribute to the risk of schizophrenia and affective disorders.

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 4.0 International license.
Back to top
PreviousNext
Posted August 05, 2016.
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.
Identification of Brain Expression Quantitative Trait Loci Associated with Schizophrenia and Affective Disorders in Normal Brain Tissue
(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
Identification of Brain Expression Quantitative Trait Loci Associated with Schizophrenia and Affective Disorders in Normal Brain Tissue
Oneil G. Bhalala, Artika P. Nath, UK Brain Expression Consortium, Michael Inouye, Christopher R. Sibley
bioRxiv 068007; doi: https://doi.org/10.1101/068007
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Identification of Brain Expression Quantitative Trait Loci Associated with Schizophrenia and Affective Disorders in Normal Brain Tissue
Oneil G. Bhalala, Artika P. Nath, UK Brain Expression Consortium, Michael Inouye, Christopher R. Sibley
bioRxiv 068007; doi: https://doi.org/10.1101/068007

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

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4116)
  • Biochemistry (8818)
  • Bioengineering (6522)
  • Bioinformatics (23466)
  • Biophysics (11793)
  • Cancer Biology (9213)
  • Cell Biology (13327)
  • Clinical Trials (138)
  • Developmental Biology (7439)
  • Ecology (11416)
  • Epidemiology (2066)
  • Evolutionary Biology (15155)
  • Genetics (10439)
  • Genomics (14045)
  • Immunology (9174)
  • Microbiology (22160)
  • Molecular Biology (8814)
  • Neuroscience (47582)
  • Paleontology (350)
  • Pathology (1429)
  • Pharmacology and Toxicology (2492)
  • Physiology (3731)
  • Plant Biology (8082)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2221)
  • Systems Biology (6039)
  • Zoology (1253)