School of Psychology and Counselling, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia.
School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia.
Acta Psychiatr Scand. 2017 Nov;136(5):493-505. doi: 10.1111/acps.12778. Epub 2017 Aug 9.
Epigenetic modifications such as DNA methylation may play a key role in the aetiology and serve as biomarkers for post-traumatic stress disorder (PTSD). We performed a genomewide analysis to identify genes whose DNA methylation levels are associated with PTSD.
A total of 211 individuals comprising Australian male Vietnam War veterans (n = 96) and males from a general population belonging to the Grady Trauma Project (n = 115) were included. Genomewide DNA methylation was performed from peripheral blood using the Illumina arrays. Data analysis was performed using generalized linear regression models.
Differential DNA methylation of 17 previously reported PTSD candidate genes was associated with PTSD symptom severity. Genomewide analyses revealed CpG sites spanning BRSK1, LCN8, NFG and DOCK2 genes were associated with PTSD symptom severity. We replicated the findings of DOCK2 in an independent cohort. Pathway analysis revealed that among the associated genes, genes within actin cytoskeleton and focal adhesion molecular pathways were enriched.
These data highlight the role of DNA methylation as biomarkers of PTSD. The results support the role of previous candidates and uncover novel genes associated with PTSD, such as DOCK2. This study contributes to our understanding of the biological underpinnings of PTSD.
表观遗传修饰，如 DNA 甲基化，可能在创伤后应激障碍（PTSD）的发病机制中发挥关键作用，并作为其生物标志物。我们进行了全基因组分析，以确定与 PTSD 相关的 DNA 甲基化水平发生改变的基因。
共纳入 211 名个体，包括澳大利亚男性越南战争老兵（n = 96）和来自 Grady 创伤项目的普通人群中的男性（n = 115）。使用 Illumina 阵列从外周血中进行全基因组 DNA 甲基化分析。使用广义线性回归模型进行数据分析。
与 PTSD 症状严重程度相关的是 17 个先前报道的 PTSD 候选基因的差异 DNA 甲基化。全基因组分析显示，跨越 BRSK1、LCN8、NFG 和 DOCK2 基因的 CpG 位点与 PTSD 症状严重程度相关。我们在一个独立的队列中复制了 DOCK2 的发现。通路分析显示，在所关联的基因中，肌动蛋白细胞骨架和黏附斑分子通路内的基因是富集的。
这些数据强调了 DNA 甲基化作为 PTSD 生物标志物的作用。结果支持了先前候选基因的作用，并揭示了与 PTSD 相关的新基因，如 DOCK2。这项研究有助于我们理解 PTSD 的生物学基础。
