Project name: Homo sapiens

Description: Aberrant DNA methylation and gene expression have been reported in postmortem brain tissues of psychotic patients, but until now there has been no systematic evaluation of synergistic changes in methylation and expression on a genome-wide scale in brain tissue. In this study, genome-wide methylation and expression analyses were performed on cerebellum samples from 39 patients with schizophrenia, 36 patients with bipolar disorder, and 43 unaffected controls, to screen for a correlation between gene expression and CpG methylation. Out of 71,753 CpG gene pairs (CGPs) tested across the genome, 204 were found to significantly correlate with gene expression after correction for multiple testing [p < 0.05, false discovery rate (FDR) q < 0.05]. The correlated CGPs were tested for disease-associated expression and methylation by comparing psychotic patients with bipolar disorder and schizophrenia to healthy controls. Four of the identified CGPs were found to significantly correlate with the differential expression and methylation of genes encoding phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1), butyrophilin, subfamily 3, member A3 (BTN3A3), nescient helix-loop-helix 1 (NHLH1), and solute carrier family 16, member 7 (SLC16A7) in psychotic patients (p < 0.05, FDR q < 0.2). Additional expression and methylation datasets wereused to validate the relationship between DNA methylation, gene expression, and neuropsychiatric diseases. These results suggest that the identified differentially expressed genes with an aberrant methylation pattern may represent novel candidate factors in the etiology and pathology of neuropsychiatric disorders.Overall design: A total of 155 postmortem cerebellum brains were used in this study, including 47 bipolar disorder, 46 schizophrenia, 15 depression patients and 47 normal controls. All were of European Ancestry. We also designed 13 random replicates in our experiment. Illumina Infinium HumanMethylation27 BeadChip was used for DNA methylation profiling. The assay was performed at the Genomics Core Facility at Northwestern University.

Data type: Epigenomics

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2012-06-22