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

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

Research output: Contribution to journalArticle

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 â '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.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalNature neuroscience
Volume19
Issue number1
DOIs
StatePublished - Dec 29 2015

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex'. Together they form a unique fingerprint.

  • Cite this