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Two gene co-expression modules differentiate psychotics and controls

Molecular Psychiatry volume 18, pages 1308–1314 (2013)Cite this article

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Abstract

Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders. Associated genetic and gene expression changes have been identified, but many have not been replicated and have unknown functions. We identified groups of genes whose expressions varied together, that is co-expression modules, then tested them for association with SCZ. Using weighted gene co-expression network analysis, we show that two modules were differentially expressed in patients versus controls. One, upregulated in cerebral cortex, was enriched with neuron differentiation and neuron development genes, as well as disease genome-wide association study genetic signals; the second, altered in cerebral cortex and cerebellum, was enriched with genes involved in neuron protection functions. The findings were preserved in five expression data sets, including sets from three brain regions, from a different microarray platform, and from BD patients. From those observations, we propose neuron differentiation and development pathways may be involved in etiologies of both SCZ and BD, and neuron protection function participates in pathological process of the diseases.

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Acknowledgements

This work was funded by 5R01MH080425 (to C.L.), and supported by the Geraldi Norton Foundation and the Eklund Family. We thank Elizabeth Thomas and Ali Torkamani for sharing Victorian Brain Bank Network (VBBN) brain expression data with us. We thank investigators of Wellcome Trust Case–Control Consortium (WTCCC) for sharing non-psychiatric disease type 2 diabetes GWAS data. We thank the investigators of Bipolar Genome Study (BiGS) for generating those bipolar GAIN-BD and Tgen-BD GWAS data, thank investigators of GAIN for generating SZ GWAS data. We thank Seth E. Dobrin, Maree Webster and other collaborators at the Stanley Medical Research Institute for providing the Stanley Online Genomics Database and brain samples. We also thank Lorenzo Pesce, Alex Rodriguez and collaborators at Computation Institute, University of Chicago for supplying their supercomputing devices and services.

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  1. Members of the Bipolar Disorder Genome Study (BiGS) Consortium are listed at the end of the article.

Authors and Affiliations

  1. Department of Psychiatry, The University of Illinois at Chicago, Chicago, IL, USA

    C Chen, L Cheng, C Zhang & C Liu

  2. Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA

    K Grennan, J A Badner & E S Gershon

  3. Department of Pediatrics, The University of Illinois at Chicago, Chicago, IL, USA

    F Pibiri

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  1. C Chen
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Members of the Bipolar Disorder Genome Study (BiGS) Consortium

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Correspondence to C Liu.

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Chen, C., Cheng, L., Grennan, K. et al. Two gene co-expression modules differentiate psychotics and controls. Mol Psychiatry 18, 1308–1314 (2013). https://doi.org/10.1038/mp.2012.146

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