TRANSMISSION AND GENETICS OF ALCOHOL DISORDERS IN A NATIVE AMERICAN TRIBE

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Using a whole genome scan, we will assess genetic linkage to alcoholism and associated psychiatric disorders in Choctaw American Indians. Choctaw is a large Eastern North American Indian tribe with over 30,000 enrolled members living within tribal boundaries in Oklahoma. By contrast to neighboring American Indian tribes that have high prevalences of alcoholism, this tribe stands out because alcoholism has a low prevalence, about 1% and 10% of females and males, respectively. By studying American Indians in the context low alcoholsim, we can expect to reveal different insights into the roles of genetic and/or environmental determinants of alcoholism. Genetic analysis is to be conducted using three samples from the tribe: a small random sample (N=100), 3 large extended families (N<80 per family), and a sample of more than 150 admixed nuclear families. The admixed nuclear familes will be selected to have some Euro-american ancestry and at leat one alcoholic family member. The transmission/disequilibrium test (TDT) is the linkage analysis method of principal interest, because it has been shown to have increased power with population admixture. However, the sampling design will also accomodate standard non-parametric two- and multi-point linkage methods. These methods will be useful for high resolution mapping of promising chromosomal regions identified by the TDT. In order to perform the analyses outlined above, individual psychiatric interviews and blood samples will be collected. Research diagnoses will be made from the psychiatric interviews and DNA for genotyping will be extracted from the blood samples. For the linkage analysis, we expect to type up to 500 short tandem repeat DNA polymorphisms spanning the entire human genome. In the past year, the random sample and extended families have been collected and the data are currently under analysis. The large study on genetically admixed families is in progress.