DNA Methylation Signatures of Peripheral Leukocytes in Schizophrenia

• DOI: 10.1007/s12017-012-8198-6
• Publication Date: 2012-09-08T03:48:53Z
• Authors: Makoto Kinoshita; Shusuke Numata; Atsushi Tajima; Shinji Shimodera; Shinji Ono; Akira Imamura; Jun-ichi Iga; Shinya Watanabe; Kumiko Kikuchi; Hiroko Kubo; Masahito Nakataki; Satsuki Sumitani; Issei Imoto; Yuji Okazaki; Tetsuro Ohmori
• Keywords: Adult; Male; 0301 basic medicine; Twins, Monozygotic; DNA Methylation; 3. Good health; Cohort Studies; Young Adult; 03 medical and health sciences; Japan; Diseases in Twins; Leukocytes; Schizophrenia; Humans; CpG Islands; DNA, Intergenic; Female; Promoter Regions, Genetic; 3' Untranslated Regions; Antipsychotic Agents

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.