The impact of traumatic stress on the methylome: implications for PTSD

创伤应激对甲基化组的影响：对 PTSD 的影响

基本信息

批准号：
9487032
负责人：
MARK W LOGUE
金额：
$ 56.12万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-18 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9487032
关键词：
Adult American Animal Model Bioinformatics Biological Markers Biological Process Blood Brain Candidate Disease Gene Cell division Child Child Abuse Clinical Complement DNA DNA Methylation DNA Sequence Alteration Data Data Set Development Diagnosis Disease Enhancers Environment Environmental Exposure Environmental Risk Factor Epigenetic Process Etiology Exposure to Fibrinogen Future Gene Expression Genes Genetic Genomics Goals Immune response Individual Intervention Life Measurement Measures Mental disorders Meta-Analysis Methylation Minority Modification Molecular National Institute of Mental Health Pathway Analysis Pathway interactions Patients Peripheral Post-Traumatic Stress Disorders Property Prospective Studies Prospective cohort Psychopathology Reporting Research Personnel Risk Factors Role Sampling Site Strategic Planning Stress Tissues Trauma Work base biomarker development biomarker performance case control clinical biomarkers cohort combat early experience epigenetic marker epigenome epigenome-wide association studies genome wide association study genome-wide immune function insight longitudinal analysis methylation pattern methylome public health relevance response sex therapeutic target trauma exposure traumatic event working group

项目摘要

DESCRIPTION (provided by applicant): 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, predicts PTSD in multiple studies, and methylation of some genes may be informative for early prediction and treatment of PTSD. The purpose of this study is to facilitate an epigenome-wide association study (EWAS) of PTSD in participating cohorts in Psychiatric Genomics Consortium (PGC) PTSD workgroup. In this study, we will leverage thousands of cross-sectional and longitudinal samples of PTSD cases and trauma-exposed controls with methylome data collected using the same genome-wide array. The meta-analyses of these samples will be allow for identification of DNA methylation patterns that predict PTSD in diverse subjects as well as those that are sex-specific or specific to type of trauma (child vs. adult or combat vs. civilian). DNA methylation patterns that are most predictive of PTSD will be replicated in an independent cohort of cases and controls. The results of this study provide insight into the biologic pathways underlying the development and progression of PTSD, will complement ongoing efforts to identify therapeutic targets for PTSD, and will inform prospective studies of PTSD and trauma exposure that are underway.

描述（由申请人提供）：目前尚不清楚为什么有些人会因创伤事件而患上创伤后应激障碍（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，在多项研究中可以预测 PTSD。一些基因的甲基化可能为 PTSD 的早期预测和治疗提供信息。本研究的目的是促进精神病基因组学参与队列中 PTSD 的表观基因组关联研究 (EWAS)。在这项研究中，我们将利用数千个 PTSD 病例和创伤暴露对照样本以及使用相同的全基因组阵列收集的甲基化数据，对这些样本进行荟萃分析。允许识别预测不同受试者的 PTSD 的 DNA 甲基化模式，以及最能预测 PTSD 的特定性别或特定创伤类型（儿童与成人或战斗与平民）的 DNA 甲基化模式。这项研究的结果将在独立的病例和对照队列中进行复制，深入了解 PTSD 发生和进展的生物学途径，将补充正在进行的确定 PTSD 治疗靶点的努力，并将为 PTSD 和 PTSD 的前瞻性研究提供信息。正在进行的创伤暴露。