3) Genotype:phenotype associations in alcoholism and related disorders.  Genetic variants that are associated with alcohol dependence and related disorders or effects such as binging, flushing, or antisocial personality disorder are being investigated.  Questions of interest include the use of recent methods to detect variants with small effect on the disease, the relationship between the presumed protective effect of flushing and prevalence of alcohol dependence, and application of methods to fetal alcohol syndrome.  Assayed variants occur in alcohol metabolism genes (ADH, ALDH) and neurological response genes (alpha-synuclein).  Native Americans suffer a disproportionately high rate of alcohol dependence relative to other U.S. populations and several populations have agreed to participate in our study.  Genetic typing and analysis is complete for two American Indian populations (Southwest and Plains).  Graduate student Becca Gray and Lindsey Williams (University Scholars fellow/undergraduate student) have recently assayed variants in alpha-synuclein, a gene that is involved in Parkinson's disease in humans and was recently implicated in alcohol consumption in a rat model.  Collaboration with Jeff Long (University of Michigan), David Goldman (NIAAA, NIH), Andrew Singleton (NIA, NIH) and Rongling Wu (University of Florida).  This work was supported by NIH grant R03 AA12906.