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Identification of genes implicated in schizophrenia by a meta-analysis of microarray gene expression studies of the human prefrontal cortex

Identification of genes implicated in schizophrenia by a meta-analysis of microarray gene expression studies of the human prefrontal cortex
Identification of genes implicated in schizophrenia by a meta-analysis of microarray gene expression studies of the human prefrontal cortex
Small cohort sizes and modest levels of gene expression changes in brain tissue have plagued the statistical approaches employed in microarray studies investigating the mechanism of schizophrenia. To combat these problems a combined analysis of six prior microarray studies was performed to facilitate the robust statistical analysis of gene expression data from the dorsolateral prefrontal cortex of 107 patients with schizophrenia and 118 healthy subjects. Multivariate permutation tests identified 144 genes that were differentially expressed between schizophrenia and control groups. Seventy of these genes were identified as differentially expressed in at least one component microarray study but none of these individual studies had the power to identify the remaining 74 genes, demonstrating the utility of a combined approach. Gene ontology terms and biological pathways that were significantly enriched for differentially expressed genes were related to neuronal cell-cell signaling, mesenchymal induction, and mitogen-activated protein kinase signaling, which have all previously been associated with the etiopathogenesis of schizophrenia. The differential expression of BAG3, C4B, EGR1, MT1X, NEUROD6, SST and S100A8 was confirmed by real-time quantitative PCR in an independent cohort using postmortem human prefrontal cortex samples. Comparison of gene expression between schizophrenic subjects with and without detectable levels of antipsychotics in their blood suggests that the modulation of MT1X and S100A8 may be the result of drug exposure. In conclusion, this combined analysis has resulted in a statistically robust identification of genes whose dysregulation may contribute to the mechanism of schizophrenia.
0022-3956
1464-1474
Perez-Santiago, J.
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Diez-Alarcia, R.
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Callado, L.F.
9d44db8e-051c-496d-8103-54eff90d1198
Zhang, J.X.
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Chana, G.
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White, C.
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Glatt, S.
84ed6ac5-ae20-4906-b496-f31a2c622204
Tsuang, M.
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Everall, I.P.
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Meana, J.J.
9e690895-2a73-4ff9-96ae-487d677da50c
Woelk, C.H.
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Perez-Santiago, J.
f949a54e-37d9-4bb2-8998-93cbad4a80f7
Diez-Alarcia, R.
51dd8a9d-134d-4543-b565-6e4869c4ae12
Callado, L.F.
9d44db8e-051c-496d-8103-54eff90d1198
Zhang, J.X.
9c53aa66-c108-4b31-97ae-4b7d05a91571
Chana, G.
166cf442-9374-499a-9be9-6d1666793241
White, C.
45233a78-f0c9-4696-8aaf-1b2673f83c91
Glatt, S.
84ed6ac5-ae20-4906-b496-f31a2c622204
Tsuang, M.
a9eb4ffd-f8a8-464f-9f12-1580a9f91191
Everall, I.P.
9eefa2d3-0c9a-49e8-a7f4-848503406530
Meana, J.J.
9e690895-2a73-4ff9-96ae-487d677da50c
Woelk, C.H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d

Perez-Santiago, J., Diez-Alarcia, R., Callado, L.F., Zhang, J.X., Chana, G., White, C., Glatt, S., Tsuang, M., Everall, I.P., Meana, J.J. and Woelk, C.H. (2012) Identification of genes implicated in schizophrenia by a meta-analysis of microarray gene expression studies of the human prefrontal cortex. Journal of Psychiatric Research, 46 (11), 1464-1474. (doi:10.1016/j.jpsychires.2012.08.005). (PMID:22954356)

Record type: Article

Abstract

Small cohort sizes and modest levels of gene expression changes in brain tissue have plagued the statistical approaches employed in microarray studies investigating the mechanism of schizophrenia. To combat these problems a combined analysis of six prior microarray studies was performed to facilitate the robust statistical analysis of gene expression data from the dorsolateral prefrontal cortex of 107 patients with schizophrenia and 118 healthy subjects. Multivariate permutation tests identified 144 genes that were differentially expressed between schizophrenia and control groups. Seventy of these genes were identified as differentially expressed in at least one component microarray study but none of these individual studies had the power to identify the remaining 74 genes, demonstrating the utility of a combined approach. Gene ontology terms and biological pathways that were significantly enriched for differentially expressed genes were related to neuronal cell-cell signaling, mesenchymal induction, and mitogen-activated protein kinase signaling, which have all previously been associated with the etiopathogenesis of schizophrenia. The differential expression of BAG3, C4B, EGR1, MT1X, NEUROD6, SST and S100A8 was confirmed by real-time quantitative PCR in an independent cohort using postmortem human prefrontal cortex samples. Comparison of gene expression between schizophrenic subjects with and without detectable levels of antipsychotics in their blood suggests that the modulation of MT1X and S100A8 may be the result of drug exposure. In conclusion, this combined analysis has resulted in a statistically robust identification of genes whose dysregulation may contribute to the mechanism of schizophrenia.

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Published date: November 2012
Organisations: Human Development & Health, Clinical & Experimental Sciences

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Local EPrints ID: 352900
URI: http://eprints.soton.ac.uk/id/eprint/352900
ISSN: 0022-3956
PURE UUID: 4dbc0bce-f673-4466-8ccb-7b33c8aaa587

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Date deposited: 23 May 2013 14:18
Last modified: 14 Mar 2024 13:58

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Contributors

Author: J. Perez-Santiago
Author: R. Diez-Alarcia
Author: L.F. Callado
Author: J.X. Zhang
Author: G. Chana
Author: C. White
Author: S. Glatt
Author: M. Tsuang
Author: I.P. Everall
Author: J.J. Meana
Author: C.H. Woelk

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