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在大量非洲裔美国人中识别和表征尼古丁依赖的遗传决定因素。这一建议建立在尼古丁依赖的协同遗传研究（COGEND）的基础上，在COGEND中，我们研究了欧洲血统的尼古丁依赖病例和非依赖吸烟对照，进行了全基因组关联研究和综合候选基因研究（Bierut et al., 2007; Saccone et al., 2007）。本项目建议确定和评估一个定义良好的非裔美国人病例对照样本，以便进行强大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），我们将把他们与我们在这里收集的样本结合起来进行遗传分析。重要的是，招募和表型测量的程序与我们之前的研究（COGEND）相似，因此该样本可以与我们在欧洲和美国样本中对尼古丁依赖的遗传研究以及其他研究者收集的其他尼古丁依赖项目相结合和比较。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吸烟对照。目标2：通过个人访谈，全面评估1000例非裔美国人尼古丁依赖病例和1000例非裔美国人非依赖吸烟对照。目的3：评估1498例尼古丁依赖病例和1259例非依赖吸烟对照中尼古丁依赖的遗传关联，这些病例是由本样本与COGEND非裔美国人样本相结合产生的。目的4：扩大遗传流行病学和相关性研究，以检查尼古丁依赖的精细表型和相关特征。识别增加尼古丁依赖风险的基因变异的努力正在开始产生重要的结果，这些结果有望带来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重点的差异，为确定尼古丁依赖的新遗传风险因素提供机会，确认现有发现，并提高我们对这一服务不足人群中与尼古丁依赖相关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基因变异的努力正在开始产生重要结果，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。这项针对非裔美国人的研究将为确定尼古丁依赖的新遗传风险因素提供机会，证实现有的发现，并提高我们对这一服务不足人群中与尼古丁依赖相关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.