The Impact of Traumatic Stress on the Methylome: implications for PTSD

创伤性应激对甲基组的影响：对 PTSD 的影响

• 批准号: 10414121
• 负责人: MARK W LOGUE
• 金额: $ 70.24万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-18 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10414121
• 关键词: Age; Autopsy; Bioinformatics; Biological; Biological Markers; Blood; Brain; Brain region; Cells; Clinical; Collaborations; Complement; Country; Cross-Sectional Studies; DNA Methylation; DNA analysis; Data; Ensure; Environmental Exposure; Epigenetic Process; Exhibits; Exposure to; Freezing; Genes; Genetic; Genotype; Longitudinal Studies; Measures; Mendelian randomization; Meta-Analysis; Metadata; Methylation; Military Personnel; Neuroglia; Neurons; Paper; Pathway interactions; Patients; Pattern; Peripheral; Persons; Post-Traumatic Stress Disorders; Prospective Studies; Quantitative Trait Loci; Reporting; Reproducibility; Research Personnel; Risk; Role; Sampling; Severities; Signal Transduction; Site; Symptoms; Testing; Tissues; Trauma; Work; base; bisulfite; brain tissue; case control; cohort; epigenetic marker; epigenome-wide association studies; genetic variant; genome-wide; insight; methylation pattern; methylome; pediatric trauma; prospective; psychiatric genomics; resilience; responders and non-responders; response; stress related disorder; symptom treatment; therapeutic target; therapy development; trauma exposure; traumatic event; traumatic stress; treatment response; whole genome

Project Summary It is not clear why some people develop posttraumatic stress disorder (PTSD) in response to a traumatic event. DNA methylation, an epigenetic mark that associates with trauma and other environmental exposures, associates with PTSD in multiple studies, and DNA methylation of some genes may be informative for early prediction and treatment of PTSD. Over the last 3 years, the Epigenetics Workgroup of the Psychiatric Genomics Consortium for PTSD (PGC-PTSD) has brought together data from 10 studies, with over 90 investigators from 10 countries to facilitate meta-analyses of DNA methylation (DNAm) data from cross- sectional and longitudinal studies of PTSD in civilian and military cohorts. In this renewal proposal, we will build on this highly productive collaboration by replicating our findings in an independent meta-analysis and performing the largest epigenome-wide association study (EWAS) to date in >4,700 subjects, characterizing PTSD-associated CpGs in postmortem brain tissue, identifying methylation quantitative trait loci (meQTLs) in blood and brain relevant to PTSD, and characterizing DNAm changes over the course of PTSD treatment. We are poised to rapidly and efficiently identify epigenetic markers informative for early prediction and treatment and to provide context to genetic variants that predict risk and resilience following traumatic events. This study, which aligns with ongoing PGC-PTSD efforts, will inform critical questions in the field related to the role of blood-based methylation patterns as clinically-informative biomarkers and the degree to which they reflect epigentic patterns in the brain; it will also provide insight into the biologic pathways underlying PTSD, complement ongoing efforts to identify therapeutic targets, and inform prospective studies of PTSD and trauma exposure that are underway.

项目摘要 目前尚不清楚为什么有些人会因创伤事件而发展创伤后应激障碍（PTSD）。 DNA甲基化是一种与创伤和其他环境暴露相关的表观遗传标记 在多项研究中与PTSD的合作伙伴，某些基因的DNA甲基化可能会提早提供信息 PTSD的预测和处理。在过去的三年中，精神科的表观遗传学工作组 PTSD的基因组学联盟（PGC-PTSD）汇集了10项研究的数据，超过90个 来自10个国家 /地区的研究人员促进了跨交叉数据的DNA甲基化（DNAM）数据的荟萃分析 PTSD在平民和军事人群中的分区和纵向研究。在此续签建议中，我们将 通过在独立的荟萃分析和 在> 4,700名受试者中进行最大的表观基因组联想研究（EWAS），表征 验尸脑组织中与PTSD相关的CPG，鉴定甲基化定量性状基因座（MEQTL） 血液和大脑与PTSD相关，并在PTSD治疗过程中表征DNAM的变化。我们 有望快速有效地识别出早期预测和治疗信息的表观遗传标记 并为创伤事件后预测风险和弹性的遗传变异提供背景。这项研究， 这与正在进行的PGC-PTSD努力保持一致，将为与该领域的关键问题提供有关与角色有关的关键问题 基于血液的甲基化模式是临床信息的生物标志物及其反映的程度 大脑中的表察模式；它还将提供有关PTSD基础生物学途径的见解， 补充为识别治疗靶标的持续努力，并为PTSD和创伤的前瞻性研究提供信息 正在进行的曝光。