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| Status |
Public on Nov 26, 2018 |
| Title |
Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality/asymmetry in schizophrenia and bipolar disorder [Affymetrix] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Although the loss or reversal of brain laterality is one of the most consistent modalities in schizophrenia (SCZ) and bipolar disorder (BD), its molecular basis remains elusive. Our limited previous studies indicated that epigenetic modifications are key to the asymmetric transcriptomes of brain hemispheres. We used whole-genome expression microarrays to profile post-mortem brain samples from subjects with SCZ, psychotic BD [BD(+)] or non-psychotic BD [BD(-)], or matched controls (n=10/group, corresponding to different brain hemispheres) and performed whole-genome DNA methylation (DNAM) profiling of the same samples (n=3-4/group) to identify pathways associated with SCZ or BD(+) and genes/sites susceptible to epigenetic regulation. qRT-PCR and quantitative DNAM analysis were employed to validate findings in larger sample sets (n=35/group). Gene Set Enrichment Analysis (GSEA) demonstrated that BMP signaling and astrocyte and cerebral cortex development are significantly (FDR q<0.25) coordinately upregulated in both SCZ and BD(+), and glutamate signaling and TGFβ signaling are significantly coordinately upregulated in SCZ. GSEA also indicated that collagens are downregulated in right versus left brain of controls, but not in SCZ or BD(+) patients, and Ingenuity Pathway Analysis predicted that TGFB2 is an upstream regulator of these genes (p=0.0012). While lateralized expression of TGFB2 in controls (p=0.017) is associated with a corresponding change in DNAM (p≤0.023), lateralized expression and DNAM of TGFB2 are absent in SCZ or BD. Loss or reversal of brain laterality in SCZ and BD corresponds to aberrant epigenetic regulation of TGFB2 and changes in TGFβ signaling, indicating potential avenues for disease prevention/treatment.
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| Overall design |
RNA samples were extracted from the dissects of post-mortem brains (Brodmann’s area 46, dorsolateral prefrontal cortex) of patients with SCZ or BD or control subjects (n=35 per group), obtained from the Stanley Medical Research Center (SMRC). The samples used in the analysis were matched for sex, ethnicity, brain laterality, age and other demographics. A subset of n=10 samples per group were used for gene expression profiling.
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| Contributor(s) |
Abdolmaleky H, Thiagalingam S |
| Citation(s) |
30468562 |
| |
| Submission date |
Sep 23, 2018 |
| Last update date |
Jun 25, 2019 |
| Contact name |
Boston University Microarray and Sequencing Resource |
| E-mail(s) |
msrdata@bu.edu
|
| Organization name |
Boston University
|
| Department |
Microarray and Sequencing Resource
|
| Street address |
72 East Concord Street, E631
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
| GPL16311 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array [CDF: Brainarray HGU133Plus2_Hs_ENTREZG 14.0.0] |
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| Samples (30)
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| This SubSeries is part of SuperSeries: |
| GSE120342 |
Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality/asymmetry in schizophrenia and bipolar disorder |
|
| Relations |
| BioProject |
PRJNA492795 |
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