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PTSD is associated with increased DNA methylation across regions ofHLA-DPB1 and SPATC1L
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.bbi.2020.10.023
Seyma Katrinli 1 , Yuanchao Zheng 2 , Aarti Gautam 3 , Rasha Hammamieh 3 , Ruoting Yang 3 , Suresh Venkateswaran 4 , Varun Kilaru 1 , Adriana Lori 5 , Rebecca Hinrichs 5 , Abigail Powers 5 , Charles F Gillespie 5 , Aliza P Wingo 6 , Vasiliki Michopoulos 5 , Tanja Jovanovic 7 , Erika J Wolf 8 , Regina E McGlinchey 9 , William P Milberg 9 , Mark W Miller 8 , Subra Kugathasan 10 , Marti Jett 3 , Mark W Logue 11 , Kerry J Ressler 12 , Alicia K Smith 13
Affiliation  

Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, avoidance, negative alterations in cognitions and mood, and arousal symptoms that adversely affect mental and physical health. Recent evidence links changes in DNA methylation of CpG cites to PTSD. Since clusters of proximal CpGs share similar methylation signatures, identification of PTSD-associated differentially methylated regions (DMRs) may elucidate the pathways defining differential risk and resilience of PTSD. Here we aimed to identify epigenetic differences associated with PTSD. DNA methylation data profiled from blood samples using the MethylationEPIC BeadChip were used to perform a DMR analysis in 187 PTSD cases and 367 trauma-exposed controls from the Grady Trauma Project (GTP). DMRs were assessed with R package bumphunter. We identified two regions that associate with PTSD after multiple test correction. These regions were in the gene body of HLA-DPB1 and in the promoter of SPATC1L. The DMR in HLA-DPB1 was associated with PTSD in an independent cohort. Both DMRs included CpGs whose methylation associated with nearby sequence variation (meQTL) and that associated with expression of their respective genes (eQTM). This study supports an emerging literature linking PTSD risk to genetic and epigenetic variation in the HLA region.

中文翻译:


PTSD 与 HLA-DPB1 和 SPATC1L 区域 DNA 甲基化增加有关



创伤后应激障碍 (PTSD) 的特点是侵入性思维、回避、认知和情绪的负面改变以及对身心健康产生不利影响的唤醒症状。最近的证据将 CpG 的 DNA 甲基化变化与 PTSD 联系起来。由于近端 CpG 簇具有相似的甲基化特征,因此识别 PTSD 相关的差异甲基化区域 (DMR) 可能会阐明定义 PTSD 差异风险和恢复力的途径。在这里,我们的目的是确定与 PTSD 相关的表观遗传差异。使用 MmethylationEPIC BeadChip 从血液样本中分析的 DNA 甲基化数据用于对 Grady 创伤项目 (GTP) 的 187 例 PTSD 病例和 367 例遭受创伤的对照进行 DMR 分析。 DMR 使用 R 包 Bumphunter 进行评估。经过多次测试校正后,我们确定了两个与 PTSD 相关的区域。这些区域位于 HLA-DPB1 的基因体和 SPATC1L 的启动子中。在一个独立队列中,HLA-DPB1 中的 DMR 与 PTSD 相关。两个 DMR 都包含 CpG,其甲基化与附近序列变异 (meQTL) 相关,并且甲基化与其各自基因的表达相关 (eQTM)。这项研究支持了一项新兴文献,该文献将 PTSD 风险与 HLA 区域的遗传和表观遗传变异联系起来。
更新日期:2021-01-01
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