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Epigenome-Wide Study of Posttraumatic Stress Disorder Symptom Severity in a Treatment-Seeking Adolescent Sample
Journal of Traumatic Stress ( IF 2.4 ) Pub Date : 2021-02-02 , DOI: 10.1002/jts.22655
Christina M Sheerin 1 , Eva E Lancaster 1, 2 , Timothy P York 1, 2 , Jesse Walker 3, 4 , Carla Kmett Danielson 3 , Ananda B Amstadter 1
Affiliation  

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.

中文翻译:

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

新兴研究表明,心理社会创伤暴露可能引发表观遗传变化,并对基因的转录调控产生下游影响。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) 相关的生物途径的有价值的工具。这项研究代表了青少年样本中 PTSD 的第一个 EWAS,考虑到这一发育时期对于 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) 包括经历过人际创伤并参加治疗研究的青少年。参与者使用 UCLA PTSD Reaction Index for DSM - IV进行评估– 青少年版并在基线时提供血样。从全血中分离基因组 DNA,并使用 Illumina Infinium MethylationEPIC BeadChip 进行分析。初步分析估计了各个 CpG 部位与 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% 时具有显着性。两个部位的低甲基化与 PTSD 症状评分增加有关。差异甲基化区域 (DMR) 的分析确定了与 FDR < 10% 的 PTSD 症状评分相关的 DMR。还讨论了后续模型的结果。这项初步调查的结果表明在青少年样本中进行进一步研究的重要性。
更新日期:2021-02-02
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