Genomics

Dataset Information

81

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. Overall design: DNA methylation data from the dorsolateral prefrontal cortex from 335 controls and 191 patients with schizophrenia. Some samples were run multiple times. The `BrNum` column delineates individual subjects and the `bestQC` column below indicates which samples to use to result in one array per subject.

INSTRUMENT(S): Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)

SUBMITTER: Andrew Jaffe  

PROVIDER: GSE74193 | GEO | 2015-10-21

SECONDARY ACCESSION(S): PRJNA299301

REPOSITORIES: GEO

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

Jaffe Andrew E AE   Gao Yuan Y   Deep-Soboslay Amy A   Tao Ran R   Hyde Thomas M TM   Weinberger Daniel R DR   Kleinman Joel E JE  

Nature neuroscience 20151130 1


DNA methylation (DNAm) is important in brain development and is potentially important 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 publis  ...[more]

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