Twin, molecular, and developmental approaches to understanding alcohol misuse

描述（由申请人提供）：整合双胞胎，分子和发展方法来理解酒精滥用：该申请申请了一个为期五年的K02奖，其总体目标是发展一个跨学科的研究项目，旨在促进我们对遗传影响如何影响酒精使用障碍发展的理解。这将通过整合双胞胎研究、基因鉴定项目和纵向社区样本的发现来完成。该研究计划有三个主要目标：(1)利用双胞胎研究来表征遗传和环境对酒精使用和相关疾病的影响的性质，重点是(a)研究遗传效应作为环境和整个发育过程的功能的变化影响，以及(b)了解遗传影响如何影响与酒精使用障碍相关的风险表型谱。第二个目的(2)是确定涉及酒精使用和相关表型的基因。第三个目标(3)是利用纵向研究的基于社区的个体样本来描述与已识别基因相关的风险，以测试与特定基因相关的影响如何在整个发育过程中以及与特定环境因素相结合时发生变化。这些目标将通过整合我资助的几个项目的数据来实现：两个基于人群的双胞胎样本，FinnTwin12和弗吉尼亚成人双胞胎精神和物质使用障碍研究；两个基因鉴定项目：酒精中毒遗传学合作研究和酒精依赖爱尔兰受影响同胞对研究；以及三个以社区为基础的纵向样本：儿童发展项目，每年对约500名5-25岁的儿童进行跟踪调查；流动青年研究，这是一项正在进行的研究，对象是来自高风险、贫困社区的10-18岁非裔美国儿童；以及雅芳父母与儿童纵向研究（Avon Longitudinal Study of Parents and Children），这是一项流行病学队列研究，从英国一个地理有限的地区招募了约10,000名儿童，并从产前到成年早期反复评估（至少每年一次）。因此，本项目整合了许多研究方法的发现，利用关于遗传影响性质的双胞胎研究（目标1）的结果，在纵向社区样本（目标3）中提出假设，以测试与特定基因（在目标2中确定）相关的风险。总之，这些研究将协同推进我们对遗传和环境因素如何共同影响酒精问题发展的理解。为了使我有能力进行所提议的分析，在两个新的内容领域提出了重点职业发展建议：(i)酒精问题的幼儿风险因素，（ii）酒精问题风险因素的种族差异，以及两个方法学领域：(i) GWAS方法学，（ii）纵向数据分析。这些直接源于我的资助项目，代表了我目前在酒精研究领域的专业知识的扩展。

DESCRIPTION (provided by applicant): Integrating Twin, Molecular, and Developmental Approaches to Understanding Alcohol Misuse: This application requests funding for a five year K02 award, with the overarching goal of developing an interdisciplinary program of research aimed at advancing our understanding of how genetic influences impact the development of alcohol use disorders. This will be accomplished by integrating findings across twin studies, gene identification projects, and longitudinal, community-based samples. The research plan has three broad aims: (1) To use twin studies to characterize the nature of genetic and environmental influences on alcohol use and related disorders, with focus on (a) studying the changing influence of genetic effects as a function of the environment and across development, and (b) understanding how genetic influences impact the phenotypic spectrum of risk associated with alcohol use disorders. The second aim (2) is to identify genes involved in alcohol use and related phenotypes. The third aim (3) is to characterize the risk associated with identified genes using community-based samples of individuals studied longitudinally, to test how the effect associated with specific genes may change across development and in conjunction with specific environmental factors. These aims will be accomplished by integrating data across several of my funded projects: two population-based twin samples, FinnTwin12 and the Virginia Adult Twin Study of Psychiatric and Substance Use disorders; two gene identification projects: the Collaborative Study on the Genetics of Alcoholism and the Irish Affected Sib Pair Study of Alcohol Dependence; and three longitudinal, community-based samples: the Child Development Project, a study of ~500 children followed annually from age 5-25; the Mobile Youth Study, an on-going study of African-American children ages 10-18 from high-risk, impoverished neighborhoods; and the Avon Longitudinal Study of Parents and Children, an epidemiological cohort of ~10,000 children enrolled from a geographically-limited region in the UK, and assessed repeatedly (minimally yearly) prenatally through young adulthood. Accordingly, this project integrates findings across a number of research approaches, using results from twin studies about the nature of genetic influences (Aim 1) to develop hypotheses to test about the risk associated with specific genes (identified in Aim 2) in longitudinal, community samples (Aim 3). Together, these studies will synergize to advance our understanding of how genetic and environmental factors come together to influence to the development of alcohol problems. To inform my ability to conduct the proposed analyses, focused career development is proposed in two new content areas: (i) early childhood risk factors for alcohol problems, and (ii) racial differences in risk factors for alcohol problems, and two methodological areas: (i) GWAS methodology, and (ii) longitudinal data analyses. These stem directly from my funded projects and represent expansions to my current areas of expertise in alcohol research. PUBLIC HEALTH RELEVANCE: The complexity of the genetics of alcohol dependence necessitates a variety of research approaches. This project integrates analyses from twin studies, used to characterize the nature of genetic influences on alcohol- related phenotypes; molecular genetic studies, aimed at gene identification; and community-based samples, used to characterize the risk associated with specific genes across development and as a function of the environment. Understanding how genetic and environmental factors interact across development will be critical to develop more effective, tailored programs of prevention and intervention.