title: DNA methylation changes in the postmortem dorsolateral prefrontal cortex of patients with schizophrenia.
abstract: BACKGROUND
  Schizophrenia is a complex psychiatric disorder with a lifetime morbidity rate of 0.5-1.0%. The pathophysiology of schizophrenia still remains obscure. Accumulating evidence indicates that DNA methylation, which is the addition of a methyl group to the cytosine in a CpG dinucleotide, might play an important role in the pathogenesis of schizophrenia.
  
  
  METHODS
  To gain further insight into the molecular mechanisms underlying schizophrenia, a genome-wide DNA methylation profiling (27,578 CpG dinucleotides spanning 14,495 genes) of the human dorsolateral prefrontal cortex (DLPFC) was conducted in a large cohort (n = 216) of well characterized specimens from individuals with schizophrenia and non-psychiatric controls, combined with an analysis of genetic variance at ~880,000 SNPs.
  
  
  RESULTS
  Aberrant DNA methylation in schizophrenia was identified at 107 CpG sites at 5% Bonferroni correction (p < 1.99 × 10(-6)). Of these significantly altered sites, hyper-DNA methylation was observed at 79 sites (73.8%), mostly in the CpG islands (CGIs) and in the regions flanking CGIs (CGI: 31 sites; CGI shore: 35 sites; CGI shelf: 3 sites). Furthermore, a large number of cis-methylation quantitative trait loci (mQTL) were identified, including associations with risk SNPs implicated in schizophrenia.
  
  
  CONCLUSIONS
  These results suggest that altered DNA methylation might be involved in the pathophysiology and/or treatment of schizophrenia, and that a combination of epigenetic and genetic approaches will be useful to understanding the molecular mechanism of this complex disorder.
authors.affiliation: Human Brain Collection Core, National Institute of Mental Health, National Institutes of Health Bethesda, MD, USA ; Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Tokushima, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Numata
authors.affiliation: The Lieber Institute for Brain Development, Johns Hopkins University Medical Center Baltimore, MD, USA.
authors.forename: Tianzhang
authors.initials: T
authors.lastname: Ye
authors.affiliation: Human Brain Collection Core, National Institute of Mental Health, National Institutes of Health Bethesda, MD, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Herman
authors.affiliation: Human Brain Collection Core, National Institute of Mental Health, National Institutes of Health Bethesda, MD, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Lipska
keywords: DNA methylation; SNP; array; expression; postmortem; schizophrenia