title: DNA methylation signatures of peripheral leukocytes in schizophrenia.
abstract: Schizophrenia (SCZ) is a complex psychiatric disease with a lifetime morbidity rate of 0.5-1.0 %. To date, aberrant DNA methylation in SCZ has been reported in several studies. However, no comprehensive studies using medication-free subjects with SCZ have been conducted. In addition, most of these studies have been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions, so little is known about the DNA methylation signatures across the whole genome in SCZ. Genome-wide DNA methylation profiling (485,764 CpG sites) of peripheral leukocytes was conducted in the first set of samples (24 medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed using three pairs of monozygotic twins that were discordant for SCZ. Finally, the data from these two independent cohorts were compared. A total of 234 differentially methylated CpG sites that were common between these two cohorts were identified. Of the 234 CpG sites, 153 sites (65.4 %) were located in the CGIs and in the regions flanking CGIs (CGI: 40.6 %; CGI shore: 13.3 %; CGI shelf: 11.5 %). Of the 95 differently methylated CpG sites in the CGIs, most of them were located in the promoter regions (promoter: 75.8 %; gene body: 14.7 %; 3'-UTR: 2.1 %). Aberrant DNA methylation in SCZ was identified at numerous loci across the whole genome in peripheral leukocytes using two independent sets of samples. These findings support the notion that altered DNA methylation could be involved in the pathophysiology of SCZ.
authors.affiliation: Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-8-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Shusuke
authors.initials: S
authors.lastname: Numata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tajima
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimodera
authors.forename: Shinji
authors.initials: S
authors.lastname: Ono
authors.forename: Akira
authors.initials: A
authors.lastname: Imamura
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Iga
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kubo
authors.forename: Masahito
authors.initials: M
authors.lastname: Nakataki
authors.forename: Satsuki
authors.initials: S
authors.lastname: Sumitani
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohmori
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D021901:DNA, Intergenic / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D007962:Leukocytes / Q000737:chemistry*; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D014430:Twins, Monozygotic; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D014150:Antipsychotic Agents; D021901:DNA, Intergenic