Dataset Information

Mapping DNA methylation across development, genotype, and schizophrenia in the human frontal cortex

ABSTRACT: DNA methylation (DNAm) is important in brain development, and potentially in schizophrenia. We characterized DNAm in prefrontal cortex from 335 non-psychiatric controls across the lifespan and 191 patients with schizophrenia, and identified widespread changes in the transition from prenatal to postnatal life. These DNAm changes manifest in the transcriptome, correlate strongly with a shifting cellular landscape, and overlap regions of genetic risk for schizophrenia. A quarter of published GWAS-suggestive loci (4,208/15,930, p<10-20) manifest as significant methylation quantitative trait loci (meQTLs), including 59.6% of GWAS-positive schizophrenia loci. We identified 2,104 CpGs that differ between schizophrenia patients and controls, enriched for genes related to development and neurodifferentiation. The schizophrenia-associated CpGs strongly correlate with changes related to the prenatal-postnatal transition and show slight enrichment for GWAS risk loci, while not corresponding to CpGs differentiating adolescence from later adult life. These data implicate an epigenetic component to the developmental origins of this disorder.

ORGANISM(S): Homo sapiens

PROVIDER: GSE74193 | GEO | 2015/10/21

SECONDARY ACCESSION(S): PRJNA299301

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Despite of multiple systematic studies of schizophrenia pathogenesis, reconstruction of the mechanism established on proteomics, metabolomics, and genome-wide significant loci is still a challenging task. We suggested that advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) may enhance the current evidence and fundamental knowledge about molecular pathogenesis of schizophrenia. Liquide chromatography and ultra-high-resolution mass-spectrometry were utilized for proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. Proteomic and metabolomic results were quantitatively evaluated and overlayed on the GWAS data. After statistical analysis using R-package, the resulting features were associated in a multilayer mode with adjusted biological processes in a reconstructed unified map of molecular events. We have identified 20 DFE proteins that were validated on an independent cohort of patients that are significant for schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. Almost half of them are new for schizophrenia. The metabolomic survey revealed 18 compounds most of which were the part transformation of tyrosine and steroids with the incline to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.) which were extracted as group-specific determinants that permits to isolate patients with schizophrenia. The GWAS assay revealed 52 loci were integrated into proteome-metabolome data as significantly implicated in schizophrenia. We integrated three layers of omics science (proteomics, metabolomics and GWAS) and quantitative analysis utilized systematic approach to reconstruct the proposed map of molecular events associated with the considered psychopathology. The resulting interplay between different layers emphasized strict implication of lipids metabolism, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones and sex hormones interconnection. The proposed interplay map can give opportunity in the understanding how the regulation of distinct metabolic axis is achieved and what happens in proteome arrangements to produce a schizophrenia-specific pattern of pathology condition.

Dataset Information

Mapping DNA methylation across development, genotype, and schizophrenia in the human frontal cortex

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets