IRPG5 R01:NOVEL PHENOTYPES FOR GENETICS OF ALCOHOLISM

印第安纳大学互动研究计划项目（IU-IRPG）是八个拟议irpg之一，其长期目标是阐明导致酒精中毒（酒精依赖）易感性和严重程度的遗传表型和潜在遗传机制。为此，将在来自不同种族人群的密集影响家族和对照家族中研究已建立的和潜在的酒精相关表型性状之间的关系及其与候选基因和数量性状位点（qtl）的关联和连锁。在拟议的研究中，将确定中枢神经系统（CNS）去抑制的定量测量的遗传力，并将其与易感和/或合并症I轴和II轴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因素，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。这些表型背后的基因将通过全基因组调查和候选基因关联研究寻求。IU-IRPG建议确定这些目标所需的遗传信息群体的公平份额，并评估它们对神经去抑制的新表型。此外，我们将使用BrAC夹紧程序来定义酒精急性反应的新表型和酒精消除率。我们将估计这些表型和定量临床表型的遗传性，这些表型与饮酒的数量-频率、耐受性、失去控制、渴望酒精和身体戒断有关。最后，我们将贡献一半的基因分型和遗传分析来检验我们的假设，并将为部分IRPG数据库提供数据管理服务。

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.