IRPG5 R01:NOVEL PHENOTYPES FOR GENETICS OF ALCOHOLISM

印第安纳州大学互动研究计划项目（IU-IRPG）是八个建议的IRPG之一，其长期目标是阐明遗传表型和潜在的遗传机制，有助于酒精中毒（酒精依赖）的易感性和严重性。 为此，建立和潜在的酒精中毒相关的表型性状之间的关系和它们的关联和候选基因和数量性状位点（QTL）的连锁将在一个队列的密集影响和控制家庭的种族多样性的人口进行了研究。 在拟定的研究中，将确定中枢神经系统（CNS）去抑制定量指标的遗传性，并将其与诱发和/或共病轴I和II精神疾病的临床诊断相关联。 中间表型被认为是酒精依赖的基本要素，将使用定量量表进行评估，确定其遗传性，并分析其与酒精中毒严重程度的关系。 这些表型的基因将通过全基因组调查和候选基因关联研究来寻找。 IU-IRPG建议确定这些目标所需的遗传信息人口的公平份额，并评估他们的神经去抑制的新表型。 此外，我们将使用BrAC钳夹程序来定义对酒精的急性反应和酒精消除率的新表型。 我们将估计这些表型和与饮酒量-频率、耐受性、失控、嗜酒和身体戒断有关的定量临床表型的遗传率。 最后，我们将贡献一半的基因分型和遗传分析所需的测试我们的假设，并将提供数据管理服务的IRPG数据库的一部分。

The Indiana University interactive research program project (IU-IRPG) is one of eight proposed IRPGs whose long-term goal is the elucidation of heritable phenotypes and underlying genetic mechanisms that contribute to alcoholism (alcohol dependence) susceptibility and severity. To this end, the relationships among established and potentially alcoholism-relevant phenotypic traits and their association and linkage to candidate genes and quantitative trait loci (QTLs) will be studied in a cohort of densely affected and control families from ethnically diverse populations. In the proposed studies, the heritability of quantitative measures of central nervous system (CNS) disinhibition will be determined and correlated with clinical diagnoses of predisposing and/or comorbid Axis I and II psychiatric disorders. Intermediate phenotypes considered to be fundamental elements of alcohol dependence will be assessed using quantitative scales, their heritability determined, and their relationship to severity of alcoholism analyzed. The genes that underlie these phenotypes will be sought through a genome wide survey and candidate gene association studies. The IU-IRPG proposes to ascertain a fair share of the genetically informative population necessary for these goals and to assess them for novel phenotypes of neural disinhibition. In addition, we will use the BrAC clamping procedure to define novel phenotypes of the acute response to alcohol and the alcohol elimination rate. We will estimate the heritability of these phenotypes and of the quantitative clinical phenotypes relating to quantity-frequency of drinking, tolerance, loss of control, craving for alcohol, and physical withdrawal. Finally we will contribute half the genotyping and genetic analyses required to test our hypotheses, and will provide data management services for portions of the IRPG database.