Genome-wide expression profiling of schizophrenia using a large combined cohort

Mistry, M., Gillis, J., Pavlidis, P. (2013) Genome-wide expression profiling of schizophrenia using a large combined cohort. Molecular Psychiatry, 18 (2). pp. 215-225. ISSN 13594184 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22212594
DOI: 10.1038/mp.2011.172

Abstract

Numerous studies have examined gene expression profiles in post-mortem human brain samples from individuals with schizophrenia compared with healthy controls, to gain insight into the molecular mechanisms of the disease. Although some findings have been replicated across studies, there is a general lack of consensus on which genes or pathways are affected. It has been unclear if these differences are due to the underlying cohorts or methodological considerations. Here, we present the most comprehensive analysis to date of expression patterns in the prefrontal cortex of schizophrenic, compared with unaffected controls. Using data from seven independent studies, we assembled a data set of 153 affected and 153 control individuals. Remarkably, we identified expression differences in the brains of schizophrenics that are validated by up to seven laboratories using independent cohorts. Our combined analysis revealed a signature of 39 probes that are upregulated in schizophrenia and 86 that are downregulated. Some of these genes were previously identified in studies that were not included in our analysis, while others are novel to our analysis. In particular, we observe gene expression changes associated with various aspects of neuronal communication and alterations of processes affected as a consequence of changes in synaptic functioning. A gene network analysis predicted previously unidentified functional relationships among the signature genes. Our results provide evidence for a common underlying expression signature in this heterogeneous disorder. © 2013 Macmillan Publishers Limited.

Item Type: Paper
Uncontrolled Keywords: gene expression microarray post-mortem brain prefrontal cortex schizophrenia adult article brain nerve cell cohort analysis controlled study down regulation female gene expression profiling gene regulatory network human major clinical study male nucleotide sequence priority journal synaptic transmission upregulation validation study
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
diseases & disorders > mental disorders
diseases & disorders > mental disorders > schizophrenia
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
CSHL Authors:
Communities: CSHL labs > Gillis Lab
Stanley Institute for Cognitive Genomics
Depositing User: Matt Covey
Date Deposited: 04 Apr 2013 13:42
Last Modified: 06 Nov 2015 21:20
PMCID: PMC3323740
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28079

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