Genetics Study of Nicotine Dependence in African Americans

描述（由申请人提供）：本项目的总体目标是确定和表征大量非裔美国人人群中尼古丁依赖的遗传决定因素。该提议建立在尼古丁依赖性的协同遗传研究（COGEND）中奠定的基础上，其中我们在基因组范围关联研究和综合候选基因研究中研究了欧洲血统的尼古丁依赖性病例和非依赖性吸烟对照（Bierut等人，2007; Saccone等人，2007年）。该项目旨在确定和评估一个明确的非裔美国人病例对照样本，以进行强有力的全基因组关联和候选基因研究。在COGEND中，我们还招募了超过757名非裔美国人（498名尼古丁依赖病例和259名非依赖吸烟对照），我们将联合收割机与我们计划在此收集的样本结合进行遗传分析。重要的是，招募和表型测量的程序与我们以前的研究（COGEND）相似，因此可以将该样本与我们在欧洲美国样本中进行的尼古丁依赖遗传研究以及其他研究者收集的其他尼古丁依赖项目进行合并和比较。该项目有4个具体目标：目标1：对目标社区样本（N= 100，000）进行电话筛查，以确定1，000例非裔美国人尼古丁依赖病例和1，000例非裔美国人非依赖性吸烟对照。目标二：通过个人访谈，全面评估1,000名非裔美国人尼古丁依赖病例和1,000名非裔美国人非依赖性吸烟对照。目标3：在本样本与COGEND非裔美国人样本联合使用后的1，498例尼古丁依赖病例和1，259例非依赖性吸烟对照中，评价尼古丁依赖的遗传相关性。目标4：扩展遗传流行病学和关联研究，以检查尼古丁依赖的精确表型和相关特征。识别增加尼古丁依赖风险的遗传变异的努力开始产生重要的结果，这些结果有望实现量身定制的风险评估，以及更有效、更有针对性的戒烟治疗。拟议的非裔美国人研究将解决研究优先事项的差异，为确定尼古丁依赖的新遗传风险因素提供机会，确认现有的研究结果，并提高我们对与尼古丁依赖相关的特征的潜在遗传风险因素的理解。公共卫生相关性：识别增加尼古丁依赖风险的遗传变异的努力开始产生重要的结果，这些结果有望实现量身定制的风险评估，以及更有效、更有针对性的戒烟治疗。拟议的非裔美国人研究将提供一个机会，以确定尼古丁依赖的新遗传风险因素，确认现有的研究结果，并提高我们对与尼古丁依赖相关的特征的潜在遗传风险因素的理解。

DESCRIPTION (provided by applicant): The overarching goal of this project is to identify and characterize genetic determinants of nicotine dependence in a large African-American population. This proposal builds on the foundation laid in the COLLABORATIVE GENETIC STUDY OF NICOTINE DEPENDENCE (COGEND), in which we studied nicotine-dependent cases and non- dependent smoking controls of European descent in a genome wide association study and a comprehensive candidate gene study (Bierut et al., 2007; Saccone et al., 2007). This project proposes to ascertain and assess a well defined African American case control sample in order to conduct robust genome-wide association and candidate gene studies. In COGEND we also recruited more than 757 African Americans (498 nicotine dependent cases and 259 non-dependent smoking controls) whom we will combine with the sample we propose to collect here for genetic analyses. Importantly, the procedures for recruitment and phenotypic measurement are similar to our previous studies (COGEND) and so this sample can be combined and compared with our genetic studies of nicotine dependence in an European American sample and other projects of nicotine dependence that have been collected by other investigators. There are 4 specific aims in this project: Aim 1: To perform a telephone screening of a targeted community sample (N=100,000) for smoking-related behavior in order to ascertain 1,000 African American nicotine-dependent cases and 1,000 African American non-dependent smoking controls. Aim 2: To comprehensively assess, through a personal interview, 1,000 African American nicotine dependent cases and 1,000 African American non-dependent smoking controls. Aim 3: To evaluate genetic associations for nicotine dependence in the 1,498 nicotine-dependent cases and 1,259 non-dependent smoking controls resulting from combination of the present sample with the COGEND African American sample. Aim 4: To expand the genetic epidemiologic and association studies to examine refined phenotypes of nicotine dependence and correlated characteristics. Efforts to identify genetic variants that increase the risk for nicotine dependence are beginning to yield important results which hold the promise of tailored risk assessment, and more effective, targeted smoking cessation treatments. The proposed study of African Americans will address the disparity in research priorities, provide an opportunity to identify novel genetic risk factors for nicotine dependence, confirm existing findings, and improve our understanding of potential genetic risk factors for characteristics correlated with nicotine dependence in this underserved population. PUBLIC HEALTH RELEVANCE: Efforts to identify genetic variants that increase the risk for nicotine dependence are beginning to yield important results which hold the promise of tailored risk assessment, and more effective, targeted smoking cessation treatments. The proposed study of African Americans will provide an opportunity to identify novel genetic risk factors for nicotine dependence, confirm existing findings, and improve our understanding of potential genetic risk factors for characteristics correlated with nicotine dependence in this underserved population.