The goal of this project is to detect the genomic location of susceptibility loci (SL) for alcoholism. Alcoholism is a chronic, progressive disorder that takes an enormous toll on health, social functioning and economic productivity, and threatens the lives of drinkers and others. The available literature provides strong evidence that genes are involved in the vulnerability to develop alcoholism. Identifying the location of these genes is the first step toward understanding their mechanism of action and developing more effective treatments. This application is for a competitive renewal to fund the genotyping and linkage analyses of the data collected under R01-AAI 1408. The first phase of the study funded the ascertainment, clinical assessment and DNA collection in Ireland of pairs of adult siblings affected with DSM-IV alcohol dependence, as well as a brief assessment and DNA collection from their parents.
The specific aims of this proposal are: I )To conduct a genome scan of a sample of 600 pairs of siblings affected with alcohol dependence; 2) To perform statistical linkage analyses of the genome scan data, using multiple phenotypes as outcomes to identify regions which may contain SL; and 3) To attempt to identify SL more precisely by following up the linkage results by identifying narrower subregions using linkage analysis, using pilot fine-scale mapping to narrow the sub-regions, based on association methods, and testing for replication in an independent sample for which high-quality clinical interview data and DNA are already available. To conduct this project we have assembled a team of experts in clinical assessment, statistical genetics and molecular genetics.
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