DNA Methylation Signatures of Peripheral Leukocytes in Schizophrenia
DNA Methylation Signatures of Peripheral Leukocytes in Schizophrenia
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DOI：
10.1007/s12017-012-8198-6
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发表时间：
2013-03-01
影响因子：
3.5
通讯作者：
Ohmori, Tetsuro
中科院分区：
文献类型：
--
作者：
Kinoshita, Makoto;Numata, Shusuke;Ohmori, Tetsuro
精神分裂症（SCZ）是一种复杂的精神疾病，终生发病率为0.5- 1.0%。迄今为止，SCZ中的异常DNA甲基化已在几项研究中报道。然而，尚未进行使用无药物SCZ受试者的全面研究。此外，这些研究大多局限于分析基因启动子区CpG岛（CGI）中的CpG位点，因此对SCZ全基因组DNA甲基化特征知之甚少。使用Infinium HumanMethylation 450 Beadchips对第一组样本（24例未用药的SCZ患者和23例非精神病对照）进行外周血白细胞的全基因组DNA甲基化分析（485，764个CpG位点）。第二，使用三对SCZ不一致的单卵双胞胎进行单卵双胞胎研究。最后，对这两个独立队列的数据进行比较。共鉴定了234个差异甲基化CpG位点，这些位点在这两个队列中是常见的。在234个CpG位点中，153个位点（65.4%）位于CGI和CGI侧翼区域（CGI：40.6%; CGI海岸：13.3%; CGI架：11.5%）。在CGIs中的95个不同甲基化的CpG位点中，它们中的大多数位于启动子区域（启动子：75.8%;基因体：14.7%; 3 '-UTR：2.1%）。使用两组独立的样本，在外周血白细胞全基因组的许多位点上鉴定出SCZ中的异常DNA甲基化。这些发现支持了DNA甲基化改变可能参与SCZ病理生理的观点。
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.