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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-01

AUTHORS

Andrew E Jaffe, Yuan Gao, Amy Deep-Soboslay, Ran Tao, Thomas M Hyde, Daniel R Weinberger, Joel E Kleinman

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. More... »

PAGES

40-47

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nn.4181

    DOI

    http://dx.doi.org/10.1038/nn.4181

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1012863491

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26619358


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