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: 10651631
• 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/10651631
• 关键词: 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; Moods; Multiomic Data; Neurosciences; Pathway Analysis; Peripheral; Phenotype; Positioning Attribute; Post-Traumatic Stress Disorders; Prevalence; Prevention; Prevention strategy; Psychiatry; Publishing; RNA; Research; Research Personnel; Residual state; Risk; Role; Sample Size; Sampling; Site; Statistical Methods; Symptoms; Tissue-Specific Gene Expression; Tissues; Training; Transcript; Trauma; Veterans; Work; bioinformatics tool; biomarker identification; collaborative environment; combat; differential expression; epigenetic marker; epigenomics; experience; functional genomics; gene network; 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的培训。 统计遗传学，功能基因组学和生物信息学，以确定分子生物标志物 创伤后应激障碍（PTSD），可以帮助监测PTSD的进展， 为美国退伍军人提供预防工作和个性化护理。为了实现这一目标，她将 使用整合的多组学研究退伍军人PTSD的表观基因组学和转录组学， approach.这项研究是创新的，因为它代表了迄今为止最大的纵向研究， 美国退伍军人PTSD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，优先考虑创伤后应激障碍的生物标志物， 整合不同的数据集。这项研究将利用现有的知识，并提供新的见解 关于PTSD的病因，需要改善美国退伍军人的医疗保健， disorder.拟议的研究和培训计划是高度互补的; Montalvo-Ortiz博士将 获得关键的新知识和技能，这将推动她的工作，包括1）纵向 全基因组DNA甲基化数据分析; 2）RNA测序分析; 3）多基因组DNA甲基化数据整合; 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。这个CDA-2赠款将加强她的神经科学培训， 在研究创伤对晚期和晚期精神障碍患者的影响时， 精神病基因组学和生物信息学的尖端技术。她的导师是由一个 在VA CT医疗保健和耶鲁大学建立的领域领先的研究人员的多学科小组。的 创新的研究和这些机构的支持和合作环境将装备 她很好地发展成为一个独立的VA研究人员与必要的工具，进行 对一些最普遍和最致残的精神疾病进行严格的综合性多组学研究， 美国退伍军人的疾病 ! !