Identifying Biomarkers of Post-traumatic Stress Disorder in U.S. Veterans using an Integrative Multi-Omics Approach

使用综合多组学方法识别美国退伍军人创伤后应激障碍的生物标志物

• 批准号: 10091302
• 负责人: Janitza Liz Montalvo-Ortiz
• 金额: --
• 依托单位: VA CONNECTICUT HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091302
• 关键词: Address; Age; Arousal; Bioinformatics; Biological Markers; Candidate Disease Gene; Chronic; Cognition; Cohort Studies; DNA; DNA Methylation; Data; Data Analyses; Data Set; Disease; Environmental Risk Factor; Epigenetic Process; Etiology; Event; Exposure to; Funding; Gene Expression; Gene set enrichment analysis; Genes; Genetic; Genome Scan; Genomics; Goals; Grant; Health; Healthcare; Healthcare Systems; Institution; Interdisciplinary Study; International; Knowledge; Lead; Learning; Linear Regressions; Longitudinal Studies; Mediation; Mendelian randomization; Mental disorders; Mentorship; Methods; Methylation; Military Personnel; Modeling; Monitor; Network-based; Neurosciences; Pathway Analysis; Peripheral; Phenotype; Positioning Attribute; Post-Traumatic Stress Disorders; Prevalence; Prevention; Prevention strategy; Psychiatry; Publishing; RNA; Research; Research Personnel; Research Training; Residual state; Role; Sample Size; Sampling; Site; Statistical Methods; Symptoms; Tissue-Specific Gene Expression; Tissues; Training; Transcript; Trauma; Veterans; Work; affective disturbance; base; bioinformatics tool; collaborative environment; combat; differential expression; disorder risk; epigenetic marker; epigenomics; experience; functional genomics; genome wide association study; genome-wide; genome-wide analysis; improved; individual variation; innovation; insight; longitudinal analysis; molecular marker; multidisciplinary; multilevel analysis; multiple omics; novel; personalized care; programs; psychiatric genomics; recruit; reference genome; resilience; saliva sample; skills; supportive environment; symposium; tool; transcriptome sequencing; transcriptomics

The ultimate goal of the CDA-2 is for Dr. Montalvo-Ortiz to obtain training in advanced methods of statistical genetics, functional genomics and bioinformatics to identify molecular biomarkers of posttraumatic stress disorder (PTSD) that can help monitor the progression of PTSD and inform prevention efforts and personalized care for U.S. veterans. To accomplish this goal, she will investigate the epigenomics and transcriptomics of PTSD in veterans using an integrative multi-omics approach. This study is innovative because it represents the largest longitudinal study, to date, of the epigenomics of PTSD in U.S. veterans, will address the causality of the epigenetic biomarkers identified, and will use cutting-edge bioinformatic methods to prioritize biomarkers for PTSD by integrating different datasets. This study will leverage current knowledge and provide novel insights on the etiology of PTSD needed to improve the healthcare for U.S. veterans that suffer from this disorder. The proposed research and training plans are highly complementary; Dr. Montalvo-Ortiz will acquire crucial new knowledge and skillsets that will advance her work to include 1) longitudinal analysis of genome-wide DNA methylation data; 2) RNA-sequencing analysis; 3) integration of multi- omics (DNA methylation-gene expression) datasets; and 4) functional genomics analysis using existing and novel bioinformatics tools. This CDA-2 grant will augment her neuroscience training and initial exposure in the study of the effects of trauma in psychiatric disorders with advanced and cutting-edge skills in psychiatric genomics and bioinformatics. Her mentorship is composed by a multidisciplinary group of established field-leading researchers at VA CT Healthcare and Yale. The innovative research and the supportive and collaborative environment of these institutions will equip her well in developing into an independent VA researcher with the tools necessary to conduct rigorous integrative multi-omics research on some of the most prevalent and disabling psychiatric disorders in U.S. veterans. ! !

CDA-2的最终目标是让Montalvo-Ortiz博士获得先进的治疗方法培训 统计遗传学、功能基因组学和生物信息学在分子生物学标志物识别中的应用 创伤后应激障碍(PTSD)，可帮助监测创伤后应激障碍的进展并向 为美国退伍军人提供预防努力和个性化护理。为了实现这一目标，她将 综合多组学研究退伍军人创伤后应激障碍的表观基因组学和转录组学 接近。这项研究具有创新性，因为它是迄今为止规模最大的纵向研究， 美国退伍军人创伤后应激障碍的表观基因组学，将解决表观遗传生物标志物的因果关系 确定，并将使用尖端的生物信息学方法来优先处理创伤后应激障碍的生物标志物 集成不同的数据集。这项研究将利用当前的知识并提供新的见解 关于创伤后应激障碍的病因需要改善美国退伍军人的医疗保健 无序。拟议的研究和培训计划具有很强的互补性；Montalvo-Ortiz博士将 获得关键的新知识和技能，这些知识和技能将推动她的工作，包括纵向 全基因组DNA甲基化数据分析；2)RNA测序分析；3)多基因整合 组学(DNA甲基化-基因表达)数据集；以及4)使用 现有的和新的生物信息学工具。这笔CDA-2拨款将加强她的神经科学培训和 首次暴露于创伤对晚期和晚期精神障碍的影响研究 精神病学基因组学和生物信息学的尖端技能。她的导师是由一位 由VA、CT Healthcare和耶鲁大学公认的领域领先研究人员组成的多学科小组。这个 创新研究以及这些机构的支持和合作环境将为 她很好地发展成为一名独立的退伍军人管理局研究员，拥有必要的工具 对一些最流行和最致残的精神病患者进行严格的综合多组学研究 美国退伍军人的精神障碍。 好了！ 好了！