Epigenome-Wide Study of Posttraumatic Stress Disorder Symptom Severity in a Treatment-Seeking Adolescent Sample.

Epigenome-Wide Study of Posttraumatic Stress Disorder Symptom Severity in a Treatment-Seeking Adolescent Sample.
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寻求治疗的青少年样本中创伤后应激障碍症状严重程度的表观基因组研究。

DOI:
10.1002/jts.22655
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发表时间:
2021-06
影响因子:
3.3
通讯作者:
Amstadter AB
Amstadter AB
中科院分区:
医学3区
文献类型:
--
作者:
Sheerin CM;Lancaster EE;York TP;Walker J;Danielson CK;Amstadter AB

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新兴研究表明,心理社会创伤暴露可能引发表观遗传变化,并对基因转录调控产生下游影响。全表观基因组关联研究 (EWAS) 提供了一种不可知的方法来检查 DNA 甲基化 (DNAm) 关联,并且是帮助识别与创伤后应激障碍 (PTSD) 相关的生物途径的宝贵工具。这项研究代表了青少年样本中第一个 PTSD 的 EWAS,考虑到这个发育时期对于 DNAm 变化和 PTSD 风险的重要性,这是一个重要的群体。样本(n = 39,M 年龄 = 15.41 岁,SD = 1.27,84.6% 女性)由经历过人际创伤并参加治疗研究的青少年组成。使用加州大学洛杉矶分校 DSM-IV 青少年版 PTSD 反应指数对参与者进行评估,并提供基线血样。从全血中分离出基因组 DNA,并使用 Illumina Infinium MmethylationEPIC BeadChip 进行检测。主要分析估计了各个 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,有两个显着的错误发现率 (FDR) < 10%。两个位点的低甲基化均与 PTSD 症状评分增加相关。对差异甲基化区域 (DMR) 的分析发现,DMR 与 FDR < 10% 的 PTSD 症状评分相关。还讨论了后续模型的结果。这项初步调查的结果表明,对青少年样本进行进一步研究的重要性。随着更多此类样本的出现,分析流程和结果将被记录下来,以便在未来的元分析工作中使用。
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.
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