TY  - JOUR
T1  - A system-level transcriptomic analysis of schizophrenia using postmortem brain tissue samples
AU  - Roussos P, Katsel P, Davis KL, Siever LJ, Haroutunian V
Y1  - 2012/12/01
N1  - 10.1001/archgenpsychiatry.2012.704
JO  - Archives of General Psychiatry
SP  - 1205
EP  - 1213
VL  - 69
IS  - 12
N2  - Context 
                  Schizophrenia is a common, highly heritable, neurodevelopmental mental illness, characterized by genetic heterogeneity.Objective 
                  To identify abnormalities in the transcriptome organization among older persons with schizophrenia and controls.Design 
                  Weighted gene coexpression network analysis based on microarray transcriptomic profiling.Setting 
                  Research hospital.Patients 
                  Postmortem brain tissue samples from 4 different cerebrocortical regions (the dorsolateral prefrontal cortex, the middle temporal area, the temporopolar area, and the anterior cingulate cortex) from 21 persons with schizophrenia and 19 controls.Main Outcome Measures 
                  Results from gene expression microarray analysis, from analysis of coexpression networks, and from module eigengene, module preservation, and enrichment analysis of schizophrenia-related genetic variants.Results 
                  The oligodendrocyte, microglial, mitochondrial, and neuronal (GABAergic and glutamatergic) modules were associated with disease status. Enrichment analysis of genome-wide association studies in schizophrenia and other illnesses demonstrated that the neuronal (GABAergic and glutamatergic) and oligodendrocyte modules are enriched for genetically associated variants, whereas the microglial and mitochondrial modules are not, providing independent support for more direct involvement of these gene expression networks in schizophrenia. Interregional coexpression network analysis showed that the gene expression patterns that typically differentiate the frontal, temporal, and cingulate cortices in controls diminish significantly in persons with schizophrenia.Conclusions 
                  These results support the existence of convergent molecular abnormalities in schizophrenia, providing a molecular neuropathological basis for the disease.
SN  - 0003-990X
M3  - doi: 10.1001/archgenpsychiatry.2012.704
UR  - http://dx.doi.org/10.1001/archgenpsychiatry.2012.704
ER  -