与PTSD相关的细胞类型特异性和炎症性DNA甲基化模式

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity Pub Date : 2025-04-24 DOI:10.1016/j.bbi.2025.04.031

Alicia K. Smith , Seyma Katrinli , Adam X. Maihofer , Allison E. Aiello , Dewleen G. Baker , Marco P. Boks , Leslie A. Brick , Chia-Yen Chen , Shareefa Dalvie , Negar Fani , Catherine B. Fortier , Joel Gelernter , Elbert Geuze , Charles F. Gillespie , Jasmeet P. Hayes , Suzi Hong , Ronald C. Kessler , Anthony P. King , Nastassja Koen , Karestan C. Koenen , Anthony S. Zannas

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引用次数: 0

摘要

包括DNA甲基化（DNAm）在内的去遗传修饰可以在创伤应激暴露下发生变化，并可能有助于区分患有和非创伤后应激障碍的个体。在这里，我们研究了创伤后应激障碍患者免疫细胞类型和炎症特异性的dna模式。方法本研究纳入了来自精神病学基因组学联盟（PGC） PTSD表观遗传学工作组的11个队列的3277名参与者。用MethylationEPIC芯片检测血液中的dna。采用标准化的QC流水线进行细胞成分的计算。在每个队列中，我们确定了与创伤后应激障碍相关的细胞类型特异性dna模式，控制性别（如果适用），年龄和血统。通过汇总统计数据进行meta分析。结果与创伤暴露对照组相比，sptsd患者的B细胞和NK细胞比例较低，中性粒细胞比例较高。总的来说，我们在六种类型的免疫细胞中鉴定了96个与ptsd相关的CpGs。这些差异大多存在于B细胞中，PTSD患者95%的B细胞甲基化水平较低。有趣的是，B细胞中注释到PTSD相关基因的CpGs在最近的PTSD GWAS中富集(p <；0.0001)。结论本研究在个体免疫细胞类型中发现了新的创伤后应激障碍相关CpGs，并支持免疫失调和炎症在创伤后应激障碍中的作用。

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

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.

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来源期刊

Brain, Behavior, and Immunity 医学-免疫学

CiteScore

29.60

自引率

2.00%

发文量

290

审稿时长

28 days

期刊介绍： Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.