与创伤后应激障碍相关的细胞类型特异性和炎症性DNA甲基化模式。

Cell-type-specific and inflammatory DNA methylation patterns associated with PTSD.

作者信息

Smith Alicia K, Katrinli Seyma, Maihofer Adam X, Aiello Allison E, Baker Dewleen G, Boks Marco P, Brick Leslie A, Chen Chia-Yen, Dalvie Shareefa, Fani Negar, Fortier Catherine B, Gelernter Joel, Geuze Elbert, Gillespie Charles F, Hayes Jasmeet P, Hong Suzi, Kessler Ronald C, King Anthony P, Koen Nastassja, Koenen Karestan C, Liberzon Israel, Linnstaedt Sarah D, McLean Samuel A, Michopoulos Vasiliki, Milberg William P, Miller Mark W, Mufford Mary S, Nugent Nicole R, Orcutt Holly K, Powers Abigail, Rauch Sheila A M, Ressler Kerry J, Risbrough Victoria B, Rutten Bart P F, Smoller Jordan W, Stein Dan J, Stein Murray B, Ursano Robert J, Verfaellie Mieke H, Vermetten Eric, Vinkers Christiaan H, Wani Agaz H, WareVinkers Erin B, Wildman Derek E, Wolf Erika J, Zhao Ying, Logue Mark W, Nievergelt Caroline M, Uddin Monica, Zannas Anthony S

机构信息

Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA; Emory University, Department of Human Genetics, Atlanta, GA, USA; Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA.

Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA.

出版信息

Brain Behav Immun. 2025 Aug;128:540-548. doi: 10.1016/j.bbi.2025.04.031. Epub 2025 Apr 24.

DOI:10.1016/j.bbi.2025.04.031

PMID:40286993

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12286750/

Abstract

BACKGROUND

Epigenetic modifications, including DNA methylation (DNAm), can change in response to traumatic stress exposure, and may help to distinguish between individuals with and without PTSD. Here, we examine the DNAm patterns specific to immune cell types and inflammation in those with PTSD.

METHODS

This study includes 3,277 participants from 11 cohorts participating in the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup. DNAm was assayed from blood with the MethylationEPIC BeadChip. A standardized QC pipeline was applied and used to impute cell composition. Within each cohort, we identified cell-type-specific DNAm patterns associated with PTSD, controlling for sex (if applicable), age, and ancestry. Meta-analyses were performed from summary statistics.

RESULTS

PTSD cases had lower proportions of B cells and NK cells as well as higher proportions of neutrophils when compared to trauma-exposed controls. Overall, we identified 96 PTSD-associated CpGs across six types of immune cells. Most of these differences were identified in B cells, with 95 % exhibiting lower methylation levels in those with PTSD. Interestingly, the PTSD-associated CpGs annotated to a gene in B cells were enriched in a recent GWAS of PTSD (p < 0.0001).

CONCLUSIONS

This study identifies novel PTSD-associated CpGs in individual immune cell types and supports the role of immune dysregulation and inflammation in PTSD.

摘要

背景

表观遗传修饰，包括DNA甲基化（DNAm），可因创伤应激暴露而发生变化，且可能有助于区分患有和未患有创伤后应激障碍（PTSD）的个体。在此，我们研究了PTSD患者中免疫细胞类型和炎症特有的DNAm模式。

方法

本研究纳入了来自11个队列的3277名参与者，这些队列参与了精神基因组学联盟（PGC）PTSD表观遗传学工作组。使用甲基化EPIC芯片从血液中检测DNAm。应用标准化的质量控制流程并用于估算细胞组成。在每个队列中，我们确定了与PTSD相关的细胞类型特异性DNAm模式，同时控制性别（如适用）、年龄和血统。根据汇总统计数据进行荟萃分析。

结果

与创伤暴露对照组相比，PTSD患者的B细胞和自然杀伤细胞比例较低，而中性粒细胞比例较高。总体而言，我们在六种免疫细胞类型中鉴定出96个与PTSD相关的CpG。其中大多数差异在B细胞中被发现，95%的差异在PTSD患者中表现为较低的甲基化水平。有趣的是，在B细胞中注释到一个基因的与PTSD相关的CpG在最近一项PTSD全基因组关联研究（GWAS）中显著富集（p < 0.0001）。