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.

项目摘要 当前K02独立科学家奖的目的是三倍：首先提供结构化职业 第二，精神病，统计和分子遗传学的发展活动，其次是我对我对 与酒精相关的表型，第三，将这些技能应用于对来自的丰富基因组数据的分析 我目前的R01，我的其他资助的项目以及我的研究所提供的其他数据。这些目标是 直接来自我的资金项目，并代表我当前专业领域的扩展。具体来说， 尽管我具备达到当前NIAAA R01的遗传目标所需的技能（AA020179“应力 - 在OEF/OIF退伍军人中诱发饮酒：战斗历史和PTSD的作用“正在进行） 增加培训以充分利用数据来提出在 酒精遗传学研究。由于我最初的培训（在候选基因设计中）遗传学领域具有 复杂的变化很大和增加（例如，基因组广泛的关联[GWAS]平台，EXOM 阵列，甲基化阵列）。这些新平台引入了许多分析复杂性，并具有 从数据清洁到分析到解释的过程中每个阶段的多个决策点 结果。因此，该K02将为我提供多个基因组数据整合和协调的技能 平台（例如序列，甲基化，表达）更好地利用（超越原始的，现在过时的目标） NIAAA R01关于基因组影响压力反应性和随后在士兵中饮酒的数据。这 AIM将通过分子和表观遗传学（包括湿lab浸入）的动手训练来实现AIM， 监督统计遗传分析与该领域的领导者，正式课程和 研讨会和K02顾问的个人辅导。此外，K02将加深我在 与酒精相关的表型的区域，除了压力引起的饮酒之外，这一直是我工作的重点 日期。将通过定向阅读，正式课程，分析实用经验来实现此目标 相关数据集（例如NIAAA R37011408“基因，环境和酒精滥用的纵向研究 在大学生中”，以及该领导者的指导（肯尼斯·肯德勒博士）。总而言之， 拟议的K02的总体目标是进一步我的多学科独立研究计划 旨在识别生物学和心理社会的风险和弹性因素本质上是创伤性的 与压力相关的疾病（酒精使用障碍[AUDS]，创伤后应激障碍[PTSD]）和翻译 在预防和干预计划中的这些发现中。 K02将为我提供受保护的时间 充分参与我概述的培训活动，使我能够合并我多样的培训背景 并以以前无法实现的方式推进我的研究计划。