The Collaborative Genetic Study of Nicotine Dependence

这是尼古丁依赖的合作遗传研究(COGEND)的重新提交，这是一项新的五年计划项目赠款，旨在检测和评估尼古丁依赖的家族和非家族原因。该计划的目标是确定决定尼古丁消费的生物机制、基因和环境特征，并使个人易于或保护个人免受疾病的发生和持续。对这些因素的更好理解将为减少或消除尼古丁依赖及其给所有社会带来的巨大健康负担提供新的、强有力的战略。受试者和家属将从三个地点的类似医疗保健组织招募：亨利·福特医院(底特律)、明尼苏达大学(明尼阿波利斯-圣彼得堡)。保罗)和华盛顿大学(圣路易斯)。有三个相互关联的研究：(1)尼古丁依赖个体家族的遗传流行病学研究；(2)尼古丁依赖的尼古丁及其相关表型的遗传连锁和候选基因研究；(3)尼古丁依赖与相关表型关系的神经药理学研究；(3)尼古丁代谢与烟草消费和依赖关系的神经药理学研究。候选基因研究包括病例对照和基于家庭的设计，以最大限度地增加权力，最大限度地减少因种族分层而产生的偏见。非洲裔美国人将被过度抽样，以提供足够的样本，用于统计消费、尼古丁代谢以及评估与这种疾病相关的多个领域的家族和非家族变量。数据管理和行政核心支持这些研究。每个项目都为项目做出了主题贡献。家庭流行病学项目阐明了环境和家庭因素，从中得出了信息量和质量的表型。连锁和候选基因研究包括全基因组调查、精细定位和病例对照以及基于家庭的候选基因研究，以确定决定尼古丁消费和易感性或对尼古丁依赖的保护的基因。它们对尼古丁依赖和烟草消费的发病率和家庭分布的影响将在大量先证者、对照组和亲属代谢中进行研究，为遗传学研究提供对疾病和内表型的生物学见解和候选基因。代谢变量将被用作家庭、人口和连锁研究的协变量。来自三个中心的一组调查人员将共同努力解开这种混乱的面纱。我们的团队包括流行病学家、遗传学家、统计学家、精神病学家、心理学家和药理学家。我们希望将这些基本的生物学和环境研究转化为战略，以减少尼古丁依赖带来的巨大健康负担。

This is a resubmission of the Collaborative Genetic study of Nicotine Dependence (COGEND), a new five-year Program Project Grant to detect and evaluate familial and non-familial causes of nicotine dependence. The goals of the program are the identification of biological mechanisms, genes and environmental features that determine nicotine consumption and predispose or protect individuals from the onset and persistence of the disorder. Improved understanding of these factors will suggest novel, powerful strategies for reducing or eliminating nicotine dependence and the massive health burden it places on all societies. Subjects and families will be recruited from comparable HMOs at three sites; The Henry Ford Hospital (Detroit), The University of Minnesota (Minneapolis-St. Paul) and Washington University (St. Louis). There are three interrelated studies: (1) a genetic epidemiology study of the families of nicotine dependent individuals, (2) a genetic linkage and candidate gene study of nicotine of nicotine dependence and related phenotypes and (3) a neuropharmacology study of the relationship between nicotine dependence and related phenotypes and (3) a neuropharmacology study of the relationship between nicotine metabolism and tobacco consumption and dependence. Candidate gene studies include case- control and family based designs to maximize power and minimize bias due to ethnic stratification. African-Americans will be over-sampled to provide a sufficient sample for statistical consumption, nicotine metabolism and assessment of familial and non-familial variables in multiple domains that are correlated with the disorder. Data management and administrative cores support these studies. Each project contributes thematically to the program. The family epidemiology project elucidates environmental and familial factors from which informative quantitative and qualitative phenotypes are derived. The linkage and candidates gene studies include a genome-wide survey, fine mapping and case-control and family based candidate gene studies to identify genes that determine nicotine consumption, and susceptibility or protection from nicotine dependence. Their effect on the incidence and familial distribution of nicotine dependence and tobacco consumption will be studied in the large of probands, controls and relatives metabolism providing biological insight into disorder and endophenotypes and candidate genes for the genetic study. Metabolic variables will be used as co-variables in the family, population and linkage studies. A team of investigators from three centers will work together to unravel this disorder. Our team includes epidemiologists, geneticists, statisticians, psychiatrists, psychologists, and pharmacologists. We hope to translate these basic biological and environmental studies into strategies to reduce the massive health burden of nicotine dependence.