GENETIC AND ENVIRONMENTAL CONTRIBUTIONS TO THE COURSE OF ALCOHOL USE IN WOMEN

遗传和环境对女性饮酒过程的影响

• 批准号: 8331051
• 负责人: CAROLYN E SARTOR
• 金额: $ 6.35万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-10 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8331051
• 关键词: GENETIC; ENVIRONMENTAL; CONTRIBUTIONS; COURSE; ALCOHOL

DESCRIPTION (provided by applicant): The PI is a clinical psychologist in the Department of Psychiatry at Washington University School of Medicine, an international leader in psychiatric research with well-established research programs in addictions and genetics. The PI is developing a program of research on genetic and environmental contributions to alcohol use and dependence rooted in a developmental psychopathology framework. Her research focuses on problem drinking behaviors and associated psychiatric disorders from the adolescent to young adult years, with an emphasis on the progression through stages of use and the rate at which those transitions occur. The role of childhood assaultive trauma in shaping the course of alcohol use disorders has figured prominently in her work in this area and will be a major focus of the proposed K-award project, which integrates her extensive experience with trauma-exposed populations (clinical as well as research experience) with behavioral genetic approaches to studying substance-related behaviors. The K08 will be instrumental in moving her toward her goal of establishing an independent R01-funded research program aimed at characterizing the course of alcohol use and alcohol use disorders in genetically-informative frameworks. This program of research will address three core issues: 1) the degree of variability in heritable and environmental influences on alcohol- related outcomes across stages of use and as contributors to the rate of transitions through these stages; 2) the extent to which the contributions of use and misuse of other substances, trauma exposure, and co-occurring psychiatric disorders to alcohol-related problems vary over time; and 3) the nature of the association between short-term patterns of drinking behaviors and current as well as future alcohol-related problems, including the consistency of this relationship across developmental periods. A second critical component of the PI's long-term career plans is to increase collaborations with researchers conducting treatment outcome studies and prevention program development to promote translational efforts of this line of research. The proposed career development plan, which will be undertaken under the guidance of mentor Dr. Andrew Heath, co-mentor Dr. Kenneth Sher, and consultants Dr. James Anthony and Dr. Phillip Wood, is designed to prepare the PI for the transition to independent investigator status through tutorials, hands-on experience conducting statistical analyses with existing data as well as data from the proposed new data collection, and formal coursework. The four major goals of the training plan are to gain expertise in genetically-informative approaches to characterizing the course of alcohol use, advance skills in longitudinal data analysis, establish a foundation in the basic principles of genetics and genomics, and develop proficiency in web-based data collection on alcohol-related behaviors. The proposed research project will address genetic and environmental contributions to two dimensions of the course of alcohol use: the rate of progression between drinking milestones, and day to day patterns in alcohol use. Their underrepresentation in alcohol-related studies makes identifying distinct vulnerabilities or patterns of use in women a challenging task. The current project focuses exclusively on female samples in an effort to address this issue. Progression through drinking milestones, specifically, the potential mediating and moderating effects of psychiatric and psychosocial risk factors (e.g., conduct disorder, depression, childhood assaultive trauma) on genetic contributions to transitions in alcohol use and dependence, will be examined in secondary analyses with retrospective reports of drinking history in two existing datasets. The first is a sample comprised of 4,417 female twins from the Missouri Adolescent Female Twin Study (MOAFTS) and 535 female participants from the Missouri Family Study, a high risk alcoholism family study oversampled for African-American ethnicity (50%); and b) 2,632 female twins from an Australian twin cohort. Day to day patterns of alcohol use will be investigated in a new web-based data collection with a subset of twin pairs (n=100), selected by childhood sexual abuse (CSA) status from MOAFTS. Brief telephone diagnostic interviews will be followed up with weekly web-based surveys of alcohol consumption and other substance use (as well as exposure to substance-using environments) administered in a daily diary format over a period of 12 weeks. An additional measure assessing trauma exposure in the previous 12 weeks will be included in the week 12 assessment. One year after completion of the web-based component of the study, participants will be re-contacted for a follow-up telephone interview covering the same domains of psychiatric and psychosocial functioning covered in the baseline interview. The 12 month follow-up will also involve recall of substance use and related behaviors reported over the 12 week assessment period in an effort to test consistency in reporting between prospective reports and retrospective summaries. Analyses will be aimed at quantifying familial liability and environmental contributions to patterns of problem alcohol use and determining whether women with CSA histories exhibit unique patterns of use. The project will provide feasibility data for an R01 application to conduct a longitudinal genetic association study of short-term patterns of alcohol and other substance use in adolescents using web-based data collection methods. By enhancing understanding of genetic and environmental contributions to the course of alcohol use and the development of problem drinking behaviors in women, the proposed K-award project will facilitate development of interventions targeting high-risk patterns of use and transition points in drinking course distinguished by elevated liability to problem alcohol use. PUBLIC HEALTH RELEVANCE: This K08 award will provide the applicant with the training and resources to establish a program of research that will inform etiological models of alcohol use disorders and prevention efforts by studying the course of alcohol use within genetically-informative frameworks. The proposed project's goal of quantifying genetic and environmental contributions to patterns of problem drinking and their variation across stages of alcohol use in women will help identify those junctures where drinking course can be most easily modified.

描述（由申请人提供）： PI 是华盛顿大学医学院精神病学系的临床心理学家，是精神病学研究领域的国际领导者，在成瘾和遗传学方面拥有完善的研究项目。 PI 正在制定一项基于发展精神病理学框架的研究计划，研究遗传和环境对酒精使用和依赖的影响。她的研究重点是从青少年到青年时期的问题饮酒行为和相关的精神疾病，重点是使用阶段的进展以及这些转变发生的速度。儿童攻击性创伤在塑造酒精使用障碍过程中的作用在她这一领域的工作中占据了突出地位，并将成为拟议的 K-award 项目的主要焦点，该项目将她在遭受创伤的人群中的丰富经验（临床和研究经验）与行为遗传学方法结合起来，以研究与物质相关的行为。 K08 将有助于推动她实现建立一个由 R01 资助的独立研究项目的目标，该项目旨在在遗传信息框架中描述酒精使用和酒精使用障碍的过程。该研究计划将解决三个核心问题：1）遗传和环境对不同使用阶段酒精相关结果的影响程度以及这些阶段的转变率的影响因素； 2) 使用和滥用其他物质、创伤暴露和同时发生的精神疾病对酒精相关问题的影响程度随时间变化的程度； 3）短期饮酒行为模式与当前和未来的酒精相关问题之间关联的性质，包括这种关系在整个发育时期的一致性。 PI长期职业计划的第二个关键组成部分是加强与进行治疗结果研究和预防计划开发的研究人员的合作，以促进这一研究领域的转化工作。拟议的职业发展计划将在导师 Andrew Heath 博士、联合导师 Kenneth Sher 博士以及顾问 James Anthony 博士和 Phillip Wood 博士的指导下进行，旨在通过教程、利用现有数据以及拟议的新数据收集中的数据进行统计分析的实践经验以及正式课程，为 PI 过渡到独立研究者身份做好准备。培训计划的四个主要目标是获得遗传信息方法方面的专业知识来描述酒精使用过程，提高纵向数据分析技能，建立遗传学和基因组学基本原理的基础，并熟练掌握基于网络的酒精相关行为数据收集。 拟议的研究项目将解决遗传和环境对饮酒过程两个维度的影响：饮酒里程碑之间的进展率以及饮酒的日常模式。她们在酒精相关研究中的代表性不足，使得识别女性的独特弱点或使用模式成为一项具有挑战性的任务。当前的项目专门关注女性样本，以努力解决这个问题。饮酒里程碑的进展，特别是精神和心理社会风险因素（例如行为障碍、抑郁、儿童攻击性创伤）对酒精使用和依赖转变的遗传贡献的潜在中介和调节作用，将在二次分析中进行检查，并在两个现有数据集中对饮酒史进行回顾性报告。第一个样本由来自密苏里州青少年女性双胞胎研究 (MOAFTS) 的 4,417 名女性双胞胎和来自密苏里州家庭研究的 535 名女性参与者组成，密苏里州家庭研究是一项对非裔美国人进行过采样的高风险酗酒家庭研究 (50%)； b) 来自澳大利亚双胞胎队列的 2,632 对女性双胞胎。日常饮酒模式将在一个新的基于网络的数据收集中进行调查，其中包括双胞胎子集（n = 100），这些双胞胎是根据 MOAFTS 的儿童性虐待（CSA）状况选择的。在简短的电话诊断访谈之后，将在 12 周内以每日日记的形式每周对饮酒和其他药物使用（以及暴露于药物使用环境）进行基于网络的调查。第 12 周的评估中将包括一项评估过去 12 周内创伤暴露情况的附加措施。研究的网络部分完成一年后，将重新联系参与者进行后续电话访谈，涵盖基线访谈中涵盖的相同精神和社会心理功能领域。 12 个月的随访还将涉及回顾 12 周评估期内报告的物质使用和相关行为，以测试前瞻性报告和回顾性摘要之间报告的一致性。分析的目的是量化家庭责任和环境对酗酒问题的影响，并确定有 CSA 历史的女性是否表现出独特的饮酒模式。该项目将为 R01 应用程序提供可行性数据，以使用基于网络的数据收集方法对青少年酒精和其他物质使用的短期模式进行纵向遗传关联研究。通过加深对遗传和环境对女性饮酒过程和问题饮酒行为发展的了解，拟议的 K-award 项目将促进针对高风险使用模式和饮酒过程中的过渡点的干预措施的制定，这些点以问题酒精使用的可能性增加为特征。 公共卫生相关性： 该 K08 奖项将为申请人提供培训和资源，以建立一个研究计划，通过在遗传信息框架内研究酒精使用过程，为酒精使用障碍的病因学模型和预防工作提供信息。拟议项目的目标是量化遗传和环境对女性饮酒问题模式的影响及其在女性饮酒不同阶段的变化，这将有助于确定最容易修改饮酒过程的关键点。