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

ABSTRACT: 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 published genome-wide association studies (GWAS)-suggestive loci (4,208 of 15,930, P < 10(-100)) 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 that were 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.

SUBMITTER: Jaffe AE

PROVIDER: S-EPMC4783176 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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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]

PMID: 26619358

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Dataset Information

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

Publications

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

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