title: Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation.
abstract: Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the present study is to identify DNA methylation markers that distinguish patients with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of peripheral leukocytes was conducted in two set of samples, a discovery set (20 medication-free patients with MDD and 19 controls) and a replication set (12 medication-free patients with MDD and 12 controls), using Infinium HumanMethylation450 BeadChips. Significant diagnostic differences in DNA methylation were observed at 363 CpG sites in the discovery set. All of these loci demonstrated lower DNA methylation in patients with MDD than in the controls, and most of them (85.7%) were located in the CGIs in the gene promoter regions. We were able to distinguish patients with MDD from the control subjects with high accuracy in the discriminant analysis using the top DNA methylation markers. We also validated these selected DNA methylation markers in the replication set. Our results indicate that multiplex DNA methylation markers may be useful for distinguishing patients with MDD from non-psychiatric controls.
authors.affiliation: a Department of Psychiatry; Course of Integrated Brain Sciences; Medical Informatics; Institute of Health Biosciences ; The University of Tokushima Graduate School ; Tokushima , Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Numata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ishii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tajima
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Iga
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Umehara
authors.forename: Manabu
authors.initials: M
authors.lastname: Fuchikami
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.forename: Shuken
authors.initials: S
authors.lastname: Boku
authors.forename: Akitoyo
authors.initials: A
authors.lastname: Hishimoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimodera
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morinobu
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohmori
mesh_terms: D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D005819:Genetic Markers; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: DNA methylation; biomarkers; blood; epigenetic; major depressive disorder; microarray; multiplex