The Collaborative Genetic Study of Nicotine Dependence

尼古丁依赖性的合作遗传学研究

• 批准号: 6365608
• 负责人: THEODORE REICH
• 金额: $ 162.43万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6365608
• 关键词: Collaborative; Genetic; Study; Nicotine; Dependence

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.

这是尼古丁依赖协作遗传学研究 (COGEND) 的重新提交，这是一项新的五年计划项目拨款，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生物机制、基因和环境特征，这些机制、基因和环境特征决定尼古丁的摄入量并预防或保护个体免受疾病的发作和持续。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、有力的策略。受试者和家庭将从三个地点的类似 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）。共有三项相互关联的研究：（1）尼古丁依赖个体家族的遗传流行病学研究，（2）尼古丁依赖及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之间关系的神经药理学研究，以及（3）尼古丁代谢与烟草消费之间关系的神经药理学研究 和依赖。候选基因研究包括病例对照和基于家庭的设计，以最大限度地提高功效并最大限度地减少种族分层造成的偏见。将对非裔美国人进行过度抽样，以便为统计消费、尼古丁代谢以及与该疾病相关的多个领域的家族和非家族变量的评估提供足够的样本。数据管理和管理核心支持这些研究。每个项目都对该计划做出了主题贡献。家庭流行病学项目阐明了环境和家庭因素，从中得出信息丰富的定量和定性表型。连锁和候选基因研究包括全基因组调查、精细绘图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以及对尼古丁依赖的易感性或保护的基因。将在大量先证者、对照和亲属代谢中研究它们对尼古丁依赖和烟草消费的发病率和家族分布的影响，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。代谢变量将用作家庭、人口和连锁研究中的协变量。来自三个中心的研究小组将共同努力解开这种疾病的谜团。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减轻尼古丁依赖带来的巨大健康负担的策略。