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

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.

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Acknowledgements

We would like to thank the groups and institutions who made their data available, including Dr Karoly Mirnics (Vanderbilt), Dr Vahram Haroutunian (Mt Sinai), the SMRI and the Harvard Brain bank. This study would not have been possible without their generosity. This work was supported by a Grant from the National Institutes of Health to PP (GM076990). MM was partly supported by the MIND Foundation of BC for Schizophrenia Research. JG is partly supported by CIHR and the Michael Smith Foundation for Health Research. PP is also supported by a career award from the Michael Smith Foundation for Health Research, a CIHR New Investigator award, and the Canadian Foundation for Innovation.

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Correspondence to P Pavlidis.

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Mistry, M., Gillis, J. & Pavlidis, P. Genome-wide expression profiling of schizophrenia using a large combined cohort. Mol Psychiatry 18, 215–225 (2013). https://doi.org/10.1038/mp.2011.172

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Keywords

  • schizophrenia
  • gene expression
  • microarray
  • post-mortem brain
  • prefrontal cortex

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