IRPG4:NOVEL PHENOTYPES FOR GENETICS OF ALCOHOLISM

酒精中毒会影响非裔美国人的社会、环境和医疗结果，并带来毁灭性的经济后果。 这项由霍华德大学互动研究计划（Howard-IRPG）提出的研究的总体目标是增加对非裔美国人酗酒和酗酒风险的遗传易感性的了解。 这项研究是基于一个概念模型，即遗传影响表现在酗酒的三个必要条件中：行为去抑制，消耗大量酒精的能力和身体依赖的发展。 行为去抑制可能与酗酒风险增加有关，而神经去抑制可能是该行为的基础。Howard-IRPG是8个已提出的IRPG位点之一，其长期目标是阐明导致酒精中毒易感性和严重性的新的可遗传表型。 使用IRPG确定标准，我们计划确定，筛选，招募，并进行确定和评估研究的队列50个密集影响的城市非洲裔美国人家庭和20个对照家庭。 这些研究将量化由特定诊断标准定义的酒精滥用和依赖高风险的表型，估计特定表型性状的遗传力，并确定其与候选基因和数量性状位点（QTL）的关联和连锁。 这些评估将包括神经去抑制的定量表型的遗传性以及与诱发和/或共病轴I和II疾病的临床诊断的相关性。 BrAC钳夹程序将用于确定对酒精的急性反应和酒精消除率的新表型。 我们将贡献一个重要的队列的非裔美国人的全基因组调查分析，候选基因关联研究和遗传多态性的测定需要测试这些假设，因为非裔美国人可能有显着的，遗传决定的差异，乙醇代谢。 此外，霍华德IRPG结合了许多招募网站和现有的科学和管理团队，以满足招募大量信息丰富的非洲裔美国人家庭的挑战;在管理类似的测试仪器和程序（如SSAGA和BrAC夹持技术）方面提供了大量现有的培训/经验;一个新的，NIH资助的GCRC的可用性，以支持BrAC夹紧共享资源的能力;和NIAAA合作少数酒精研究中心的现有行政和科学基础设施。 这些研究将通过与所有拟议的IRPG成员研究中心的重要互动来完成。

Alcoholism affects social, environmental and medical outcomes in African Americans with devastating economic consequences. The overall goal of the research proposed by the Howard University Interactive Research Program (Howard-IRPG) is to increase understanding of the genetic susceptibility to alcoholism and alcoholism risk among African Americans. The research is based on the conceptual model that genetic influence is manifest in each of three conditions necessary for alcoholism: behavioral disinhibition, the capacity to consume large quantities of alcohol, and the development of physical dependence. Behavioral disinhibition may be associated with increased risk for alcoholism and neural disinhibition may underlie the behavior. The Howard-IRPG is one of eight proposed IRPG sites whose long- term goal is the elucidation of novel heritable phenotypes that contribute to alcoholism susceptibility and severity. Using the IRPG ascertainment criteria, we plan to identify, screen, recruit, and perform ascertainment and assessment studies on a cohort of 50 densely affected urban African American families and 20 control families. These studies will quantify phenotypes of high risk of alcohol abuse and dependence as defined by specific diagnostic criteria, estimate the heritability of specific phenotypic traits and determine their association and linkage to candidate genes and quantitative trait loci (QTLs). These assessments will include the heritability of quantitative phenotypes of neural disinhibition and the correlation with clinical diagnoses of predisposing and/or co-morbid Axis I and II disorders. The BrAC clamping procedure will be used to define novel phenotypes of the acute response to alcohol and the alcohol elimination rate. We will contribute a significant cohort of African Americans for a genome wide survey analysis, candidate gene association studies and the determination of genetic polymorphism required to test these hypotheses since African Americans may have significant, genetically-determined differences in ethanol metabolism. In addition, The Howard IRPG combines the availability of many recruitment sites and an existing scientific and administrative team to meet the challenge of recruiting large numbers of informative African American families; offers substantial existing training/experience in the administration of similar test instruments and procedures such as the SSAGA and the BrAC clamping technique; availability of a new, NIH-funded GCRC with the ability to support the BrAC clamping Shared Resource; and the existing administrative and scientific infrastructure of a NIAAA Collaborative Minority Alcohol Research Center. These studies will be accomplished through significant interaction with all of the proposed IRPG member sites.