Biometric and Measured Genetic Research on Smoking

吸烟的生物识别和测量基因研究

• 批准号: 7116288
• 负责人: GARY E SWAN
• 金额: $ 47.02万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116288
• 关键词: behavioral genetics; clinical research; smoking; statistics /biometry

DESCRIPTION (provided by applicant): The long-range objective of this Program Project is to engender a better understanding of the factors that contribute to heightened susceptibility to smoking and nicotine dependence, using a Nicotine Research Consortium as the vehicle for coordinating and sustaining research activity derived from several independent NIH projects. Specific aims are (a) to identify highly heritable, latent factors (endophenotypes) to characterize the course and causes of smoking behavior more accurately; (b) to use twin genetic methods to estimate the heritability (proportion of variance accounted for) of endophenotypes; and (c) to test endophenotypes for association with particular candidate genes. Systematic investigations will be carried out using both biometric and measured genetic approaches in the context of three related projects: Project A, Behavioral genetics of nicotine reactivity, will attempt to quantify the genetic contribution to nicotine-dependent smoking in concordant and discordant (monozygotic and dizygotic; MZ/DZ) twins and their siblings, focusing on initial sensitivity to nicotine and chronic tolerance as phenotypic indicators. Project B, Behavioral phenotypes and environmental factors for tobacco use, examines the contribution of genetic and environmental sources of variation for smoking along dimensions of dependence, lifetime tobacco use milestones and trajectories, and composite phenotypes in a series of psychometric studies and behavior genetic studies in concordant and discordant MZ/DZ twins, in order to identify endophenotypes. Project C, Candidate genes for smoking in related and unrelated individuals, will involve an examination of ~60 susceptibility genes for smoking in (a) unrelated smokers and never-smokers using a case-control design and (b) in smokers and their biological parents using a parent-child trio design to determine genetic association with endophenotypes identified in Projects A and B. Three cores support the activities of the projects: The Administrative Core, the coordinating center for the Nicotine Research Consortium, is responsible for communication, integration, and quality control. The Analytical Chemistry Core will conduct analyses of biological samples (nicotine, cotinine, hydroxy-cotinine) from each project. The Data Management and Analysis Core will provide organized statistical design, warehousing of phenotype and genotype data, and advanced genetic analyses. Health relatedness. The proposed Program Project constitutes a systematic investigation of how individual biological, behavioral, and environmental factors come together and interact to create tobacco dependence. Identification of environmental and behavioral risk factors and more accurate characterization of phenotypes and genotypes for smoking constitute crucial next steps in the elucidation of underlying mechanisms for smoking. Such knowledge will confer new insights about the etiology and progression of smoking and should improve the current understanding of smoking, which is still largely descriptive.

描述（由申请人提供）： 该计划项目的长期目标是更好地了解导致吸烟和尼古丁依赖敏感性增加的因素，使用尼古丁研究联盟作为协调和维持来自几个独立NIH项目的研究活动的工具。具体目标是：（a）鉴定高度遗传的潜在因素（内表型），以更准确地描述吸烟行为的过程和原因;（B）使用双胞胎遗传方法估计内表型的遗传力（方差占比）;（c）测试内表型与特定候选基因的关联。将在三个相关项目的背景下使用生物测定和测量遗传方法进行系统研究：项目A，尼古丁反应性的行为遗传学，将试图量化一致和不一致（单卵和双卵; MZ/DZ）双胞胎及其兄弟姐妹中尼古丁依赖性吸烟的遗传贡献，重点关注尼古丁的初始敏感性和慢性耐受性作为表型指标。项目B，烟草使用的行为表型和环境因素，在一系列心理测量学研究和行为遗传学研究中，在一致和不一致的MZ/DZ双胞胎中，沿着沿着依赖性、终生烟草使用里程碑和轨迹以及复合表型等维度，检查遗传和环境变异源对吸烟的贡献，以确定内在表型。项目C，相关和无关个体中吸烟的候选基因，将涉及（a）使用病例对照设计检查无关吸烟者和从不吸烟者中的约60个吸烟易感基因，以及（B）使用亲子三重设计检查吸烟者及其生物学父母中的约60个吸烟易感基因，以确定与项目A和B中鉴定的内表型的遗传关联。三个核心支持项目的活动：行政核心，尼古丁研究联盟的协调中心，负责沟通，整合和质量控制。分析化学核心将对每个项目的生物样本（尼古丁、可替宁、羟基可替宁）进行分析。数据管理和分析核心将提供有组织的统计设计，表型和基因型数据的仓储，以及先进的遗传分析。健康相关性。拟议的计划项目构成了一个系统的调查，个人的生物，行为和环境因素如何走到一起，相互作用，创造烟草依赖。识别环境和行为风险因素以及更准确地表征吸烟的表型和基因型是阐明吸烟潜在机制的关键下一步。这些知识将带来关于吸烟的病因和进展的新见解，并应改善目前对吸烟的理解，这在很大程度上仍然是描述性的。