Twin, molecular, and developmental approaches to understanding alcohol misuse

理解酒精滥用的双生、分子和发育方法

• 批准号: 7771434
• 负责人: DANIELLE M DICK
• 金额: $ 12.24万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7771434
• 关键词: Address; Adolescence; Adult; Affect; African American; Age; Aggressive behavior; Alabama; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcohols; Architecture; Area; Attention deficit hyperactivity disorder; Behavior; Behavioral; Characteristics; Child; Child Development; Childhood; Cognitive; Communities; Complex; Conduct Disorder; Data; Data Analyses; Data Collection; Dependence; Development; Development Plans; Diagnosis; Disease; Enrollment; Environment; Environmental Risk Factor; Epidemiology; Funding; General Population; Genes; Genetic; Genotype; Goals; Home environment; Impulsivity; Independent Scientist Award; Individual; Interview; Longitudinal Studies; Measures; Methodology; Minority; Molecular; Molecular Genetics; Mothers; National Institute on Alcohol Abuse and Alcoholism; Nature; Neighborhoods; Oppositional Defiant Disorder; Parent-Child Relations; Parenting behavior; Parents; Pathway interactions; Pattern; Peer Group; Peer Review; Phenotype; Population; Preventive Intervention; Problem behavior; Request for Applications; Research; Research Design; Research Project Grants; Research Support; Risk; Risk Factors; Role; Sales; Sampling; Social support; Structure; Substance Use Disorder; Susceptibility Gene; Symptoms; Temperament; Testing; Time; Twin Multiple Birth; Twin Studies; Virginia; Youth; addiction; adolescent substance use; alcohol misuse; alcohol related problem; alcohol research; alcohol use disorder; anti social; base; career; career development; clinical Diagnosis; cohesion; cohort; design; deviant; early childhood; early onset substance use; externalizing behavior; genetic analysis; genetic association; genetics of alcoholism; genome wide association study; high risk; high school; indexing; parental monitoring; peer; population based; pregnant; programs; pubertal timing; public health relevance; racial difference; self esteem; stem; teacher; trait; underage drinking; young adult

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.

描述（由申请人提供）：整合双胞胎，分子和发育方法以理解酒精滥用：该申请要求为五年K02奖项提供资金，其总体目标是制定跨学科研究计划，旨在促进我们对遗传影响如何影响酒精使用障碍的发展的理解。这将通过整合双胞胎研究，基因识别项目和纵向基于社区的样本的发现来实现。该研究计划具有三个广泛的目的：（1）使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）研究遗传效应的变化作为环境和跨发育的函数的变化，以及（b）了解遗传影响如何影响与酒精使用疾病相关的遗传型影响与酒精使用相关的表型。第二个目的（2）是鉴定涉及酒精使用和相关表型的基因。第三个目的（3）是使用纵向研究的个体的基于社区的基因样本来表征与已识别基因相关的风险，以测试与特定基因相关的效果如何在整个发育过程中以及与特定的环境因素结合使用。这些目标将通过在我的几个资金项目中整合数据来实现：两个基于人群的双胞胎样本Finntwin12和弗吉尼亚成人双胞胎对精神病和药物使用障碍的研究；两个基因鉴定项目：关于酒精中毒遗传学和爱尔兰影响的SIB对酒精依赖研究的合作研究；以及三个基于社区的纵向样本：儿童发展项目，每年5-25岁开始对500名儿童进行研究；流动青年研究是一项正在进行的研究，对高风险，贫困社区的10-18岁非裔美国儿童的持续研究；以及对父母和孩子的雅芳纵向研究，这是一个从英国一个地理上有限的地区招收的约10,000名儿童的流行病学队列，并反复（每年）在成年期间反复（每年一次）（每年）进行评估。因此，该项目使用有关遗传影响的性质（AIM 1）的两种研究的结果来整合多种研究方法的发现（AIM 1），以测试纵向，社区样本中与特定基因相关的风险（AIM 2）（AIM 3）。这些研究将共同​​提高我们对遗传和环境因素如何融合影响酒精问题的发展的理解。为了告知我进行拟议的分析的能力，提出了两个新的内容领域的重点职业发展：（i）酒精问题的幼儿危险因素，以及（ii）酒精问题危险因素的种族差异以及两个方法论领域：（i）GWAS方法论和（ii）纵向数据分析。这些直接源于我的资金项目，并代表了我当前的酒精研究专业知识领域的扩展。 公共卫生相关性：酒精依赖遗传学的复杂性需要各种研究方法。该项目整合了双胞胎研究的分析，用于表征遗传影响对酒精相关表型的性质。旨在基因鉴定的分子遗传研究；和基于社区的样本，用于表征与环境之间的特定基因相关的风险。了解遗传和环境因素如何在整个发展中相互作用对于制定更有效，定制的预防和​​干预计划至关重要。