Identification of epistatic loci that influence alcohol dependence

A two-wave genome scan of informative families in the COGA has located chromosomal regions suggestive of linkage on chromosomes 1, 2, 7, 3, 15 and 16. Some of these loci (i.e. 3,16) were only identified in either waves 1 or 2 but not both. Taken together the magnitude of the effects of these loci does not seem to account for the heritable variation of alcohol dependence, suggesting that other genetic sources of variation are present. Accordingly, a search for two-locus epistatic interactions was conducted using an extension of methods (Holmans) developed by Cox et al. The search for epistatic interactions analyzed chromosomal regions, two at a time, using the initial genome scan to select regions of interest. Nuclear family and extended pedigree data were included in separate analyses. The phenotypes studied were a wide and a narrow diagnosis of Alcohol Dependence and the phenotype "alcohol dependence and habitual smoking". Preliminary evidence for epistatic interactions was found on chromosomes 1 and 15 with alcohol dependence, and on chromosomes 2 and 15 for the joint phenotype, "Alcohol Dependence and Habitual Smoking". These findings confirm and extend the initial reports of linkage on these chromosomes.