IRPG (NOVEL PHENOTYPES)

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。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。HU互动研究计划（Howard-IRPG）提出的这项研究的总体目标是增加对非裔美国人酗酒和酗酒风险遗传易感性的了解。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，神经去抑制可能是行为的基础。霍华德IRPG是八个建议IRPG网站，其长期目标是阐明新的遗传表型，有助于酒精中毒的易感性和严重性之一。使用IRPG确定标准，我们计划确定，筛选，招募和执行一个队列的50个受影响的城市非洲裔美国人家庭和20个对照家庭的确定和评估研究。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。这些评估将包括数量表型和神经去抑制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。霍华德将为全基因组调查分析，候选基因关联研究和测试这些假设所需的遗传多态性的确定贡献一个重要的非裔美国人队列，因为非裔美国人在乙醇代谢方面可能具有显着的遗传决定差异。此外，Howard 0 IRPG结合了许多招募网站和现有的科学和管理团队的可用性，以应对招募大量信息丰富的非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，以及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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alcoholism affects social, environmental and medical outcomes in African Americans with devastating economic consequences. The overall goal of the research proposed by the HU Interactive Research Program (Howard-IRPG) is to increase the 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 of 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 assessment will include heritability of quantitative phenotypes and 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. Howard 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 Howard0IRPG combines the availability of many recruitment sites and an existing scietific and administrative team to meet the challenge of recruiting large numbers of informative African American families; offers substantial existing training/experiences in the administration of similar tests 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.