IRPG4:NOVEL PHENOTYPES FOR GENETICS OF ALCOHOLISM

Howard University, Washington DC

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Abstract

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.