Abstract
Schizophrenia and bipolar disorder 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, i.e. co-expression modules, then tested them for association with schizophrenia. Using Weighted Gene Co-expression Network Analysis, we show that two modules were differentially expressed in patients versus controls. One, up-regulated in cerebral cortex, was enriched with neuron differentiation and neuron development genes, as well as disease GWAS 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 bipolar disorder patients. From those observations, we propose neuron differentiation and development pathways may be involved in etiologies of both schizophrenia and bipolar disorder, and neuron protection function participates in pathological process of the diseases.
Highlights
Schizophrenia (SCZ) and bipolar disorder (BD) are psychiatric disorders with world-wide lifetime prevalences of around 1%.1–4 These disorders have been shown to be highly heritable by monozygotic and dizygotic twin studies and by adoption studies: the heritability estimates for SCZ range from 70 to 85% and, for BD, from 60 to 85%.5 Over the past 2 decades, genetic studies of thousands of samples have identified hundreds of candidate genes.[6,7,8] Most of these findings have not been supported by genome-wide studies
We first confirmed that the M1A and M3A in parietal cortex (PCX) were well-preserved in the BD case– control data sets (Table 1; Supplementary Figures 6 and 7), we tested whether NOTCH2 and MT1X gene expression were associated with BD
We looked for case–control differences at the level of gene coexpression regulation, rather than the level of individual genes
Summary
Schizophrenia (SCZ) and bipolar disorder (BD) are psychiatric disorders with world-wide lifetime prevalences of around 1%.1–4 These disorders have been shown to be highly heritable by monozygotic and dizygotic twin studies and by adoption studies: the heritability estimates for SCZ range from 70 to 85% and, for BD, from 60 to 85%.5 Over the past 2 decades, genetic studies of thousands of samples have identified hundreds of candidate genes.[6,7,8] Most of these findings have not been supported by genome-wide studies. The method was first applied to a psychiatric disease by Torkamani et al.,[19] who detected SCZ-associated gene coexpression modules in one microarray data analysis, and found that aging affected gene expression in normal controls, but not in SCZ patients.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
