Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
J Trauma Stress. 2021 Jun;34(3):607-615. doi: 10.1002/jts.22655. Epub 2021 Feb 2.
Emerging research has demonstrated that psychosocial trauma exposure may elicit epigenetic changes, with downstream effects on the transcriptional regulation of genes. Epigenome-wide association studies (EWAS) offer an agnostic approach to examine DNA methylation (DNAm) associations and are a valuable tool to aid in the identification of biological pathways involved in posttraumatic stress disorder (PTSD). This study represents the first EWAS of PTSD in an adolescent sample, an important group given the significance of this developmental period regarding both DNAm changes and PTSD risk. The sample (n = 39, M age = 15.41 years, SD = 1.27, 84.6% female) comprised adolescents who experienced interpersonal trauma and were enrolled in a treatment study. Participants were assessed using the UCLA PTSD Reaction Index for DSM-IV-Adolescent Version and provided a blood sample at baseline. Genomic DNA was isolated from whole blood and assayed using the Illumina Infinium MethylationEPIC BeadChip. The primary analysis estimated the associations among individual CpG sites and PTSD symptom scores. Of the 793,575 screened probes tested, two were significant at a false discovery rate (FDR) < 10%. Hypomethylation of both sites was associated with increased PTSD symptom scores. Analysis of differentially methylated regions (DMR) identified a DMR associated with PTSD symptom scores at an FDR < 10%. Results from follow-up models are also discussed. Findings from this preliminary investigation suggest the importance of further research conducted in adolescent samples. The analytic pipeline and results are documented for use in future meta-analytic work as more such samples become available.
新兴研究表明，心理社会创伤暴露可能会引发表观遗传变化，从而对基因的转录调控产生下游影响。全基因组关联研究（EWAS）提供了一种探究 DNA 甲基化（DNAm）关联的无偏方法，是帮助确定创伤后应激障碍（PTSD）相关生物途径的有价值工具。本研究代表了青少年 PTSD 患者的首次 EWAS，鉴于该发育阶段在 DNAm 变化和 PTSD 风险方面的重要性，青少年是一个重要群体。该样本（n = 39，M 年龄 = 15.41 岁，SD = 1.27，84.6%为女性）由经历人际创伤并参加治疗研究的青少年组成。参与者使用 UCLA PTSD 反应指数 DSM-IV-青少年版进行评估，并在基线时提供血液样本。从全血中提取基因组 DNA，并使用 Illumina Infinium MethylationEPIC BeadChip 进行检测。主要分析估计了个体 CpG 位点与 PTSD 症状评分之间的关联。在测试的 793,575 个筛选探针中，有两个在错误发现率（FDR）<10%时具有统计学意义。这两个位点的低甲基化与 PTSD 症状评分的增加有关。差异甲基化区域（DMR）分析确定了一个与 PTSD 症状评分相关的 FDR<10%的 DMR。还讨论了后续模型的分析结果。这项初步研究的结果表明，在青少年样本中进行进一步研究的重要性。分析管道和结果记录下来，以备将来有更多此类样本时进行元分析工作。
