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

• 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
• 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

 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在创伤事件后会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，在多项研究中预测PTSD，某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一个表观基因组的关联研究（EWAS）的PTSD参与队列中的精神病基因组学联盟（PGC）的PTSD研究。在这项研究中，我们将利用数千个PTSD病例和创伤暴露对照的横截面和纵向样本，使用相同的全基因组阵列收集甲基化组数据。这些样本的荟萃分析将允许识别DNA甲基化模式，这些模式预测不同受试者的PTSD，以及那些性别特异性或特定于创伤类型（儿童与成人或战斗与平民）的模式。最能预测PTSD的DNA甲基化模式将在一个独立的病例和对照组中复制。这项研究的结果提供了对PTSD发展和进展的生物学途径的深入了解，将补充正在进行的确定PTSD治疗靶点的努力，并将为正在进行的PTSD和创伤暴露的前瞻性研究提供信息。