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：
9334946
负责人：
MARK W LOGUE
金额：
$ 55.91万
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/9334946
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 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 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 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（由应用程序提供）：尚不清楚为什么有些人会响应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，可预测多项研究中的PTSD，某些基因的甲基化可能是帮助PTSD的早期预测和治疗的信息。这项研究的目的是促进PTSD在参与精神病学基因组学联盟（PGC）PTSD Workgroup参与队列中的全基因组协会研究（EWAS）。在这项研究中，我们将利用使用相同全基因组阵列收集的甲基化数据的PTSD病例的数千个横截面和纵向样本和受创伤暴露的对照。这些样品的荟萃分析将被允许鉴定DNA甲基化模式，这些模式可以预测各种受试者的PTSD以及针对性特异性或特异性创伤类型的DNA甲基化模式（儿童与成人或战斗与平民）。最可预测PTSD的DNA甲基化模式将在独立的病例和对照组中复制。这项研究的结果提供了对PTSD发育和发展基础的生物学途径的洞察力，将补充持续的努力，以确定PTSD的治疗靶标，并将为正在进行的PTSD和创伤性外伤的前瞻性研究提供信息。