The goal of this research is to identify and describe genes that have an effect on the alcoholism phenotype. Although extensive excellent data exist supporting a genetic background for alcoholism, little is known about the exact nature of those genetic polymorphisms forming the basis of this effect. We propose to probe the relationship between certain genetic polymorphisms and phenotypes related to alcoholism, and to collect a large sample for future family- association studies useful for investigating these relationships in the future. We will pursue this goal through the following strategy. (1) Collection of a haplotype relative risk sample. Family association methods provide a valid way to test for genotype-phenotype correlation without risk of false positive results from population stratification. We will collect a sample of 165 alcohol dependent subjects and their 330 parents for haplotype relative risk candidate gene association studies. Genes to be studied include dopamine system genes (e.g. DRD2 and DRD4) and serotonin system genes. (2)Correlation of genetic data with other phenotype data such as personality measures. For example, the DRD4*7R allele has been reported by two groups to associate to novelty-seeking personality. We propose to evaluate this relationship in a sample of alcoholic subjects. This work all builds on the HRR sample.
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