The major goal of this collaborative study is to elucidate the genetic mechanisms which are related to the predisposition for alcohol abuse and dependence. A multicenter multidimensional approach is essential due to the clinical and potential genetic heterogeneity in alcohol abuse and dependence, and because phenotypic family assessment requires a comprehensive approach that utilizes a variety of expertise and experience. This proposal for a """"""""participating center"""""""" involves six separate sites specifically recruited because of the strengths of each research group. The following institutions have agreed to participate in this collaborative study: State University of New York Health Science Center at Brooklyn, NY, Indiana University School of Medicine, Indianapolis, IN, University of Connecticut Health Center, Farmington, CT, University of California, San Diego, CA in conjunction with the Scripps Clinic & Research Foundation. La Jolla, CA and Washington University School of Medicine, St. Louis, MO. In addition to the five aforementioned sites the Intramural Research Program at the National, Institute of Alcohol Abuse and Alcoholism represents the sixth site. We plan to select a subset of 300 large families (approximately 15 members per family) from an initial set of 600 families with an alcoholic proband. A uniform ascertainment and assessment protocol will be used for all family members at each site, using procedures which will yield standardized clinical and biological data across all sites. In addition to families with an alcoholic proband we will also conduct identical studies in """"""""control families"""""""" without the presence of alcohol abuse or alcoholism. The studies of """"""""control families"""""""" will be used to establish a normative data set for electrophysiological and blood markers. Age-regressed norms will be obtained with this data set. We also propose to conduct yearly retest of individuals who have not entered the age of risk (electrophysiological and blood markers, clinical assessment including alcohol and drug history) in order to assess the stability and predictability of our potential biological markers. We will conduct segregation analysis as well as a genetic linkage study using candidate genes and Restriction Fragment Length Polymorphisms.
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