Genome-wide expression profiling of schizophrenia using a large combined cohort
Open Access
- 3 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 18 (2), 215-225
- https://doi.org/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.This publication has 60 references indexed in Scilit:
- Meta-analysis indicates that common variants at the DISC1 locus are not associated with schizophreniaMolecular Psychiatry, 2011
- Gene Expression and Genetic Variation Data Implicate PCLO in Bipolar DisorderBiological Psychiatry, 2011
- A cross-laboratory comparison of expression profiling data from normal human postmortem brainNeuroscience, 2010
- Whole-genome association mapping of gene expression in the human prefrontal cortexMolecular Psychiatry, 2010
- Molecular profiles of schizophrenia in the CNS at different stages of illnessBrain Research, 2008
- Meta-analysis of two genome-wide association studies of bipolar disorder reveals important points of agreementMolecular Psychiatry, 2008
- InnateDB: facilitating systems‐level analyses of the mammalian innate immune responseMolecular Systems Biology, 2008
- Molecular Evidence for Increased Expression of Genes Related to Immune and Chaperone Function in the Prefrontal Cortex in SchizophreniaBiological Psychiatry, 2007
- Transitive functional annotation by shortest-path analysis of gene expression dataProceedings of the National Academy of Sciences of the United States of America, 2002
- BLAT—The BLAST-Like Alignment ToolGenome Research, 2002