Two gene co-expression modules differentiate psychotics and controls
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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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Another study confirmed that a dysregulated neuronal differentiation module was consistently observed in schizophrenia post-mortem brains and suggested the same pathways were involved in bipolar disorder.
“Another study confirmed that a dysregulated neuronal differentiation module was consistently observed in schizophrenia post-mortem brains and suggested that the same pathways were involved in bipolar disorder108.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [108]
Prior work has identified differential activation of glial and neural-immune processes in brains of patients with psychiatric disorders.
“Previous work has identified differential activation of glial and neural-immune processes in brain from patients with psychiatric disorders (16, 52, 57, 66–69)”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [52]
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- Authors
- Chen, C., Cheng, L., Grennan, K., Pibiri, F., Zhang, C., Badner, J. A., Members of the Bipolar Disorder Genome Study (BiGS) Consortium, Gershon, E. S., & Liu, C.
- Affiliations
- University of Illinois Chicago (US)
- University of Chicago (US)
- Corresponding author
- Liu, C
- Venue
- Molecular Psychiatry
- Published
- 2012-11-13
- Volume
- 18
- Issue
- 12
- Pages
- 1308-1314
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC4018461
- OpenAlex
- W2039032007
- Cited by
- 157
- References
- 52
- Citations by year
- 2026: 8 · 2025: 1 · 2024: 8 · 2023: 16 · 2022: 11 · 2021: 18 · 2020: 15 · 2019: 8 · 2018: 16 · 2017: 11 · 2016: 15 · 2015: 12 · 2014: 12 · 2013: 6
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Stanley Medical Research Institute
- University of Chicago
- Wellcome Trust
- Translational Genomics Research Institute
- Victorian Brain Bank
- National Institute of Mental Health (R01 MH103340, R01MH080425, R21MH083521)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- schizophrenia, bipolar disorder, gene co-expression modules, weighted gene co-expression network analysis, cerebral cortex, cerebellum, neuronal differentiation, neuronal development, brain gene expression, etiology
- MeSH terms
- Adult, Aged, Bipolar Disorder, Cell Differentiation, Cerebellum, Cerebral Cortex, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Neural Pathways, Schizophrenia, Up-Regulation, Case-Control Studies, Genetic Predisposition to Disease, Oligonucleotide Array Sequence Analysis, Genome-Wide Association Study, Young Adult
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