DNA methylation in the superior temporal gyrus of 44 subjects with schizophrenia and 44 non-psychiatric control subjects
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ABSTRACT:
PROVIDER: PRJNA605294 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation (DNAm) signal from the planum temporale of superior temporal gyrus (STG) of forty-four subjects with schizophrenia (SZ) and forty-four non-psychiatric control (NPC) subjects was measured on the Illumina MethylationEPIC BeadChip Infinium (EPIC) array. Averaged, normalized beta-values at each site were correlated with dendritic spine density (DSD) previously measured per subject to identify site-specific DNAm-DSD correlations that met methylome-wide significance, or a suggestive-level of significance. We tested the hypothesis that DNAm correlates with DSD in human STG at several sites across the methylome and that this relationship is disrupted in SZ. DSD measures were available for 40 of the subjects with SZ and 40 of the NPC subjects. We found DNAm to correlate with DSD at more sites than expected by chance in NPC, but not SZ, subjects. In addition, we show that the slopes of the linear DNAm-DSD correlations differed between SZ and NPC subjects at more sites than expected by chance. Together, these data suggest that alterations in the intercation between DNAm and neurobiology in SZ may be a mechanism for SZ-related DSD reductions.
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Project description:The miRNA microarray expression data used in this study was derived using the commercial BeadArray-based miRNA microarray platform (Illumina). The data set contained 211 RNA samples from peripheral blood mononuclear cells (PBMC) as described previously, including 128 schizophrenia subjects and 83 non-psychiatric controls. As each miRNA array matrix held 96 sample arrays, the samples were distributed into four array matrices.
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Project description:Schizophrenia is a complex psychiatric disorder encompassing a range of symptoms and etiology dependent upon the interaction of genetic and environmental factors. Several risk genes, such as DISC1, have been associated with schizophrenia as well as bipolar disorder (BPD) and major depressive disorder (MDD), consistent with the hypothesis that a shared genetic architecture could contribute to divergent clinical syndromes. The present study compared gene expression profiles across three brain regions in post-mortem tissue from matched subjects with schizophrenia, BPD or MDD and unaffected controls. Post-mortem brain tissue was collected from control subjects and well-matched subjects with schizophrenia, BPD, and MDD (n=19 from each group). RNA was isolated from hippocampus, Brodmann Area 46, and associative striatum and hybridized to U133_Plus2 Affymetrix chips. Data were normalized by RMA, subjected to pairwise comparison followed by Benjamini and Hochberg False Discovery Rate correction (FDR). Samples derived from patients with schizophrenia exhibited many more changes in gene expression across all brain regions than observed in BPD or MDD. Several genes showed changes in both schizophrenia and BPD, though the magnitude of change was usually larger in schizophrenia. Several genes that have variants associated with schizophrenia were found to have altered expression in multiple regions of brains from subjects with schizophrenia. Continued evaluation of circuit-level alterations in gene expression and gene-network relationships may further our understanding of how genetic variants may be influencing biological processes to contribute to psychiatric disease. Pre-frontal cortex, striatum and hippocampus were obtained from subjects with schizophrenia, bipolar disorder, major depressive disorder and matched controls.
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