Stress-induced drinking in Returning Soldiers: Genetic and Epigenetic Mechanisms

归国士兵压力引起的饮酒：遗传和表观遗传机制

• 批准号: 8752520
• 负责人: ANANDA B AMSTADTER
• 金额: $ 12.86万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8752520
• 关键词: Acute; Address; Adult; Affect; Alcohol consumption; Alcohol dependence; Alcohols; Area; Award; Behavioral; Behavioral Genetics; Biological Assay; Blood Pressure; Candidate Disease Gene; Clinical; Clinical Research; Collaborations; Collection; Commit; Corticotropin; Data; Data Collection; Data Set; Data Sources; Development; Development Plans; Distress; Educational workshop; Environment; Epidemiology; Epigenetic Process; Event; Faculty; Foundations; Freedom; Funding; Genes; Genetic; Genetic Markers; Genetic Research; Genetic Transcription; Genetic Variation; Genomics; Goals; Human; Hydrocortisone; Immersion Investigative Technique; Independent Scientist Award; Individual; Institutes; Interdisciplinary Study; Knowledge; Laboratories; Laboratory Study; Letters; Literature; Longitudinal Studies; Measures; Mediating; Mentorship; Methylation; Military Personnel; Molecular; Molecular Genetics; National Institute on Alcohol Abuse and Alcoholism; Nature; Neurosecretory Systems; Patient Self-Report; Pattern; Peer Review; Phenotype; Physiological; Population; Post-Traumatic Stress Disorders; Prevention program; Preventive Intervention; Procedures; Psychologist; Public Health; Reading; Recording of previous events; Recruitment Activity; Research; Research Support; Risk; Role; Science; Scientist; Serum; Societies; Soldier; Solid; Staging; Stress; Structure; Study Section; Time; Training; Training Activity; Training Support; Translations; Trauma; Trier Social Stress Test; Veterans; Virginia; Work; alcohol misuse; alcohol research; alcohol response; alcohol use disorder; biological adaptation to stress; career; career development; combat; computerized data processing; cooking; cost; design; distress tolerance; drinking; drinking behavior; epigenetic marker; exome; experience; genetic analysis; genome wide association study; intervention program; meetings; multidisciplinary; neglect; operation; prevent; programs; psychogenetics; psychosocial; public health relevance; research and development; resilience; response; skills; stem; stressor; success; university student

Project Summary The purpose of the present K02 Independent Scientist Award is threefold: first, to provide structured career development activities in psychiatric, statistical, and molecular genetics, second, to deepen my knowledge of alcohol-related phenotypes, and third, to apply these skills to the analysis of the rich genomic data yielded from my current R01, my other funded projects, as well as other data available at my institute. These goals stem directly from my funded projects and represent expansions in my current areas of expertise. Specifically, although I have the skill set needed to meet the genetic Aim of my current NIAAA R01 (AA020179 "Stress- induced Drinking in OEF/OIF Veterans: the Role of Combat History and PTSD" which is ongoing) I need increased training to fully utilize the data to ask new and deeper questions that are on the cutting edge of alcohol genetics research. Since my original training (in candidate gene designs) the field of genetics has changed significantly and increased in sophistication (e.g., genome wide association [GWAS] platforms, exom arrays, methylation arrays). These new platforms have introduced a number of analytic complexities, with multiple decision points in every stage of the process, from data cleaning to analysis to the interpretation of results. Thus, this K02 will give me the skills in the integration and harmonization of genomic data on multiple platforms (e.g., sequence, methylation, expression) to better utilize (beyond the original, now outdated aim) my NIAAA R01 data on the genomic influences on stress reactivity and subsequent alcohol use in soldiers. This aim will be achieved by hands-on training in molecular and epigenetics (including wetlab immersions), supervised statistical genetic analyses done in collaboration with leaders in the field, formal coursework and workshops, and individual tutoring by K02 consultants. Additionally, the K02 will deepen my expertise in the area of alcohol-related phenotypes, beyond stress-induced drinking, which has been the focus of my work to date. This aim will be achieved through directed readings, formal coursework, practical experience analyzing relevant datasets (e.g., NIAAA R37011408 "A Longitudinal Study of Genes, Environment and Alcohol Misuse in College Students"), and mentorship from leaders in the field (Dr. Kenneth Kendler). In summary, the overarching goal of the proposed K02 is to further my multidisciplinary independent program of research which aimed at the identification of risk and resilience factors, both biologic and psychosocial in nature, for traumatic stress related conditions (alcohol use disorders [AUDs], posttraumatic stress disorder [PTSD]) and translation of these findings into prevention and intervention programming. The K02 will provide me with protected time to fully engage in the training activities I have outlined, enabling me to coalesce my diverse training background and move my research program forward in ways not previously possible.

项目概要 设立K02独立科学家奖的目的有三个：第一，提供结构化的职业生涯 第二，加深我在精神病学、统计和分子遗传学方面的知识 与酒精相关的表型，第三，将这些技能应用于分析产生的丰富基因组数据 我当前的 R01、我的其他资助项目以及我所在研究所提供的其他数据。这些目标源于 直接来自我资助的项目，代表了我当前专业领域的扩展。具体来说， 尽管我拥有满足当前 NIAAA R01 的遗传目标所需的技能（AA020179“压力- OEF/OIF 退伍军人中的诱导饮酒：战斗历史和 PTSD 的作用”（正在进行中）我需要 加强培训，充分利用数据提出前沿的新的、更深层次的问题 酒精遗传学研究。自从我最初接受训练（候选基因设计）以来，遗传学领域已经 显着变化并提高复杂性（例如，全基因组关联 [GWAS] 平台、外显子组 阵列、甲基化阵列）。这些新平台引入了许多分析复杂性， 从数据清理到分析再到解释，流程的每个阶段都有多个决策点 结果。因此，这个 K02 将为我提供整合和协调多个基因组数据的技能。 平台（例如序列、甲基化、表达）以更好地利用（超出最初的、现在已经过时的目标）我的 NIAAA R01 关于基因组对士兵应激反应和随后饮酒的影响的数据。这 目标将通过分子和表观遗传学的实践培训（包括湿实验室沉浸）来实现， 与该领域的领导者合作进行监督统计遗传分析、正式课程作业和 研讨会以及 K02 顾问的个人辅导。此外，K02 将加深我在以下领域的专业知识： 除了压力引起的饮酒之外，与酒精相关的表型领域也是我工作的重点 日期。这一目标将通过定向阅读、正式课程、实践经验分析来实现 相关数据集（例如，NIAAA R37011408“基因、环境和酒精滥用的纵向研究 大学生”），以及该领域领导者（肯尼思·肯德勒博士）的指导。总而言之， 拟议的 K02 的总体目标是进一步推进我的多学科独立研究计划， 旨在识别创伤性风险和复原力因素，包括生物学和心理社会性质 压力相关病症（酒精使用障碍 [AUD]、创伤后应激障碍 [PTSD]）和翻译 将这些发现纳入预防和干预规划。 K02 将为我提供受保护的时间 充分参与我概述的培训活动，使我能够融合我多样化的培训背景 并以以前不可能的方式推进我的研究计划。