Collaborative Studies on the Genetics of Alcoholism/COGA

描述（由申请人提供）：酒精中毒遗传学合作研究（COGA）的主要目标是定位，鉴定和表征影响酒精依赖和相关表型的基因。一个主要的重点是继续确定基因的变异影响酗酒和相关疾病的风险。这包括识别成人中的其他基因，包括测试其他研究和多项研究联合分析的结果。与此相关的是变异体作用的分子和细胞机制的表征。另一个主要重点是对青少年和年轻人的研究，以检查整个发育过程中的遗传效应，并了解影响这一关键年龄段遗传风险表达的环境因素。这将通过一项前瞻性研究进行，在这项研究中，参与者将被仔细评估许多行为和神经表型。其中一个重要部分是开发与酗酒风险和大脑功能相关的新型行为和神经生理表型，这有助于识别相关基因并了解它们的工作机制。我们将检验这一假设，即影响成人酗酒风险和相关表型的基因也影响青少年的相关表型。我们还将测试这一假设，即在关键发育阶段暴露于酒精会导致改变基因表达的表观遗传修饰，从而影响酒精中毒及其后遗症的长期风险。支持这些努力的将是维持高质量的数据库和生物材料，并将其提供给经批准的外部研究者。这些目标从识别变异影响酒精中毒风险的基因，到了解它们如何在多个水平上发挥作用，从分子和细胞到行为，神经生理和表型水平作为发育的函数。我们预计，通过描绘有助于酒精依赖和酒精使用和滥用的途径和基因，我们将直接影响成功治疗酒精问题的能力，并干预那些风险最大的人。公共卫生相关性：酗酒是一个主要的社会和健康问题。据估计，滥用酒精每年给美国造成超过1800亿美元的损失，酒精是西方国家残疾调整生命年损失的第三大原因。了解遗传变异如何影响酒精中毒的风险将对预防和治疗这一严重疾病做出重要贡献。

DESCRIPTION (provided by applicant): The main goal of the Collaborative Study on the Genetics of Alcoholism (COGA) is to localize, identify and characterize genes influencing alcohol dependence and related phenotypes. A primary focus is to continue to identify genes in which variants affect the risk for alcoholism and related disorders. This includes identifying additional genes in adults, including testing the results from other studies and from joint analyses of multiple studies. Related to this is the characterization of the molecular and cellular mechanisms through which the variants act. Another major focus is the study of adolescents and young adults, to examine genetic effects across development and to understand the environmental factors that affect expression of genetic risk in this critical age range. This will be carried out through a prospective study in which participants are carefully assessed for many behavioral and neural phenotypes. An important part of this is the development of novel behavioral and neurophysiological phenotypes related to risk for alcoholism and to brain functions, which can help both in identifying relevant genes and understanding the mechanisms through which they work. We will test the hypothesis that genes affecting risk for alcoholism and related phenotypes in adults also affect related phenotypes in adolescents. We will also test the hypothesis that exposure to alcohol during key developmental stages causes epigenetic modifications that alter gene expression thereby affecting the long-term risk for alcoholism and its sequelae. Supporting these efforts will be the maintenance of high quality databases and biological materials, and making these available to approved external investigators. Together these aims go from identifying genes in which variants affect risk for alcoholism to understanding how they act at multiple levels, from molecular and cellular to behavioral, neurophysiological and phenotypic levels as a function of development. We anticipate that through the delineation of the pathways and genes contributing to alcohol dependence and alcohol use and abuse, we will directly impact the ability to successfully treat alcohol problems and intervene in those at greatest risk. PUBLIC HEALTH RELEVANCE: Alcoholism is a major social and health problem. It has been estimated that misuse of alcohol costs the US over $180 billion per year, and that alcohol is the third leading cause of loss of disability adjusted life years in Western countries. Understanding how genetic variations affect the risk for alcoholism will make important contributions to prevention and treatment of this serious disease.