Comprehensive survey of CNVs influencing gene expression in the human brain and its implications for pathophysiology

Mehta, Divya, Iwamoto, Kazuya, Ueda, Junko, Bundo, Miki, Adati, Naoki, Kojima, Toshio and Kato, Tadafumi (2014) Comprehensive survey of CNVs influencing gene expression in the human brain and its implications for pathophysiology. Neuroscience Research, 79 1: 22-33. doi:10.1016/j.neures.2013.10.009


Author Mehta, Divya
Iwamoto, Kazuya
Ueda, Junko
Bundo, Miki
Adati, Naoki
Kojima, Toshio
Kato, Tadafumi
Title Comprehensive survey of CNVs influencing gene expression in the human brain and its implications for pathophysiology
Journal name Neuroscience Research   Check publisher's open access policy
ISSN 0168-0102
1872-8111
Publication date 2014
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.neures.2013.10.009
Open Access Status DOI
Volume 79
Issue 1
Start page 22
End page 33
Total pages 12
Place of publication Shannon, Co. Clare Ireland
Publisher Elsevier Ireland Ltd
Collection year 2015
Language eng
Abstract Copy number variations (CNVs) contribute to neuropsychiatric diseases, which may be partly mediated by their effects on gene expression. However, few studies have assessed the influence of CNVs on gene expression in the brain. The objective was to perform an unbiased comprehensive survey of influence of CNVs on gene expression in human brain tissues. CNV regions (CNVRs) were identified in 72 individuals (23 schizophrenia, 23 bipolar disorder and 26 controls). Significant associations between the CNVRs and gene expression levels were observed for 583 CNVR-expression probe pairs (293 unique eCNVRs and 429 unique transcripts), after corrections for multiple testing and controlling the effect of the number of subjects with CNVRs by label swapping permutations. These CNVRs affecting gene expression (eCNVRs) were significantly enriched for rare/low frequency (p=1.087×10-10) and gene-harboring CNVRs (p=1.4×10-6). Transcripts overlapping CNVRs were significantly enriched for glutathione metabolism and oxidative stress only for cases but not for controls. Moreover, 72 (24.6%) of eCNVRs were located within the chromosomal aberration regions implicated in psychiatric-disorders: 16p11.2, 1q21.1, 22q11.2, 3q29, 15q11.2, 17q12 and 16p13.1. These results shed light on the mechanism of how CNVs confer a risk for psychiatric disorders.
Keyword Bipolar disorder
Genomics
Human post-mortem brains
Schizophrenia
Transcriptome
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
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Created: Fri, 24 Oct 2014, 16:57:32 EST by Sylvie Pichelin on behalf of Queensland Brain Institute