Genetics Study of Nicotine Dependence in African Americans

描述(由申请者提供)：该项目的首要目标是在大量非裔美国人中识别和描述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合作遗传研究(COGEND)奠定的基础上，在该研究中，我们在全基因组关联研究和全面的候选基因研究中研究了尼古丁依赖病例和欧洲后裔的非依赖吸烟控制(Bierut等人，2007年；萨科内等人，2007年)。该项目建议确定和评估一个定义明确的非裔美国人病例对照样本，以便进行强有力的全基因组关联和候选基因研究。在COGEND，我们还招募了超过757名非裔美国人(498例尼古丁依赖病例和259例非依赖吸烟控制病例)，我们将把他们与我们建议在这里收集的样本结合起来进行基因分析。重要的是，招募和表型测量的程序与我们之前的研究(COGEND)类似，因此可以将此样本与我们在欧洲美洲样本中对尼古丁依赖的基因研究以及其他研究人员收集的其他尼古丁依赖项目进行比较。该项目有4个具体目标：目标1：对目标社区样本(N=100,000)进行与吸烟有关的行为的电话筛查，以确定1,000例非洲裔美国人尼古丁依赖病例和1,000名非洲裔美国人不依赖吸烟控制。目标2：通过个人访谈，全面评估1000名非洲裔美国人尼古丁依赖病例和1000名非洲裔美国人非依赖型吸烟控制。目的：评估1,498例尼古丁依赖病例和1,259例非依赖吸烟对照病例中尼古丁依赖的遗传相关性，这些病例是本样本与COGEND非裔美国人样本的组合。目的4：扩大遗传流行病学和关联性研究，以检测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，这些结果有望进行量身定制的风险评估，并更有效地进行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，提供一个机会来确定尼古丁依赖的新的遗传风险因素，确认现有的发现，并提高我们对这一服务不足的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.