Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins.
Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins.
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DOI：
10.1038/tp.2015.49
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发表时间：
2015-04-28
影响因子：
6.8
通讯作者：
Fañanás L
中科院分区：
文献类型：
--
作者：
Córdova-Palomera A;Fatjó-Vilas M;Gastó C;Navarro V;Krebs MO;Fañanás L
抑郁症已被证明受到环境致病因素的高度影响，其中一些被认为是通过表观遗传修饰对人类大脑功能施加压力。先前关于抑郁症的全基因组甲基化研究表明，沿着差异DNA甲基化，同卵（MZ）对的受影响的双胞胎增加了DNA甲基化变异性，这可能与表观遗传随机性理论一致。然而，这种变异性的潜在生物根源在很大程度上仍未得到探索。本研究旨在评估同卵双生子中DNA甲基化差异是否与其精神病理状态的差异有关。来自Illumina Infinium HumanMethylation 450 Beadchip的数据用于评估34对双胞胎（17对MZ对）的外周血DNA甲基化。使用两种分析策略来鉴定（a）差异甲基化探针（DMP）和（B）差异甲基化探针（VMP）。大多数DMPs位于先前与神经精神表型相关的基因中。值得注意的是，其中一个DMPs（cg01122889）位于WDR 26基因中，该基因的DNA序列与全基因组关联研究中的重度抑郁症有关。WDR 26的表达也被认为是人类血液中抑郁症的生物标志物。互补地，VMPs位于基因如CACNA1C、IGF2和p38 MAP激酶MAPK11中，显示富集生物过程如糖皮质激素信号传导。这些结果扩展了以前的研究，表明差异甲基化和差异变异性在抑郁症的病因学和临床表现中起作用，并为抑郁症表观遗传学中潜在的特定基因组位点提供了线索。
Depressive disorders have been shown to be highly influenced by environmental pathogenic factors, some of which are believed to exert stress on human brain functioning via epigenetic modifications. Previous genome-wide methylomic studies on depression have suggested that, along with differential DNA methylation, affected co-twins of monozygotic (MZ) pairs have increased DNA methylation variability, probably in line with theories of epigenetic stochasticity. Nevertheless, the potential biological roots of this variability remain largely unexplored. The current study aimed to evaluate whether DNA methylation differences within MZ twin pairs were related to differences in their psychopathological status. Data from the Illumina Infinium HumanMethylation450 Beadchip was used to evaluate peripheral blood DNA methylation of 34 twins (17 MZ pairs). Two analytical strategies were used to identify (a) differentially methylated probes (DMPs) and (b) variably methylated probes (VMPs). Most DMPs were located in genes previously related to neuropsychiatric phenotypes. Remarkably, one of these DMPs (cg01122889) was located in the WDR26 gene, the DNA sequence of which has been implicated in major depressive disorder from genome-wide association studies. Expression of WDR26 has also been proposed as a biomarker of depression in human blood. Complementarily, VMPs were located in genes such as CACNA1C, IGF2 and the p38 MAP kinase MAPK11, showing enrichment for biological processes such as glucocorticoid signaling. These results expand on previous research to indicate that both differential methylation and differential variability have a role in the etiology and clinical manifestation of depression, and provide clues on specific genomic loci of potential interest in the epigenetics of depression.
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影响因子：
3.5
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
通讯作者：
Mill J
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
10.6
作者：
Dempster EL;Wong CC;Lester KJ;Burrage J;Gregory AM;Mill J;Eley TC
通讯作者：
Eley TC
影响因子：
3.7
作者：
Chang SC;Koenen KC;Galea S;Aiello AE;Soliven R;Wildman DE;Uddin M
通讯作者：
Uddin M
影响因子：
11.1
作者：
Feinberg, A. P.
通讯作者：
Feinberg, A. P.