The Collaborative Genetic Study of Nicotine Dependence

这是尼古丁依赖的协同遗传研究（COGEND）的再次提交，这是一项新的五年计划项目资助，旨在检测和评估尼古丁依赖的家族性和非家族性原因。该项目的目标是确定决定尼古丁摄入量的生物机制、基因和环境特征，并使个体易患或保护个体免受这种疾病的发作和持续。对这些因素的进一步了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出新颖、有力的战略。受试者和家庭将从三个地点的可比hmo中招募；亨利福特医院（底特律），明尼苏达大学(明尼阿波利斯-圣。保罗)和华盛顿大学（圣路易斯）。相关研究有三个方面：(1)尼古丁依赖个体家族的遗传流行病学研究；(2)尼古丁依赖与相关表型的尼古丁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族的设计，以最大化权力和最小化种族分层造成的偏见。非裔美国人将被过度抽样，为统计消费、尼古丁代谢和评估与该疾病相关的多个领域的家族性和非家族性变量提供足够的样本。数据管理和行政核心支持这些研究。每个项目都对项目的主题做出贡献。家庭流行病学项目阐明了环境和家族因素，从这些因素中获得了信息丰富的定量和定性表型。联系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族的候选基因研究，以确定决定尼古丁消耗的基因，以及对尼古丁依赖的易感性或保护。它们对尼古丁依赖和烟草消费的发生率和家族分布的影响将在大量先证者、对照者和亲属代谢中进行研究，为遗传研究提供对疾病和内表型以及候选基因的生物学见解。代谢变量将作为协变量用于家庭、人群和连锁研究。来自三个研究中心的一组调查人员将共同努力解开这种疾病。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。我们希望将这些基础的生物学和环境研究转化为减少尼古丁依赖带来的巨大健康负担的策略。

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.