Numata Shusuke, Ishii Kazuo, Tajima Atsushi, Iga Jun-ichi, Kinoshita Makoto, Watanabe Shinya, Umehara Hidehiro, Fuchikami Manabu, Okada Satoshi, Boku Shuken, Hishimoto Akitoyo, Shimodera Shinji, Imoto Issei, Morinobu Shigeru, Ohmori Tetsuro
a Department of Psychiatry; Course of Integrated Brain Sciences; Medical Informatics; Institute of Health Biosciences ; The University of Tokushima Graduate School ; Tokushima , Japan.
Epigenetics. 2015;10(2):135-41. doi: 10.1080/15592294.2014.1003743. Epub 2015 Jan 14.
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.
先前已有多项研究报道了重度抑郁症（MDD）患者血液中存在异常DNA甲基化。然而，尚未有针对未用药的MDD患者进行的全面研究。此外，这些先前的研究大多局限于对基因启动子区域中CpG岛（CGIs）内的CpG位点进行分析。本研究的主要目的是识别能够区分MDD患者与非精神科对照者的DNA甲基化标志物。使用Infinium HumanMethylation450 BeadChips对两组样本进行外周血白细胞全基因组DNA甲基化谱分析，一组为发现集（20例未用药的MDD患者和19例对照者），另一组为复制集（12例未用药的MDD患者和12例对照者）。在发现集中，在363个CpG位点观察到了显著的DNA甲基化诊断差异。所有这些位点在MDD患者中的DNA甲基化水平均低于对照者，并且其中大多数（85.7%）位于基因启动子区域的CGIs中。在使用顶级DNA甲基化标志物进行的判别分析中，我们能够以高精度区分MDD患者与对照者。我们还在复制集中验证了这些选定的DNA甲基化标志物。我们的结果表明，多重DNA甲基化标志物可能有助于区分MDD患者与非精神科对照者。
