Alcoholism is a common heterogenous disease. Heritability has been established in both men and women, but as for other psychiatric diseases, it has proved difficult to map genes directly for reasons such as genetic heterogeneity, phenocopies, penetrance and expressivity, and polygenic effects. We have employed an indirect approach by identifying a trait- specific marker for alcoholism vulnerability, the low voltage alpha (LVA) EEG, a normal variant of the resting EEG in which the alpha rhythm is virtually absent. This phenotype is heritable, reproducible in each individual, present in 4-11% of the population and accurately determined. We now have a complete data set, including EEG and ERP phenotypes, blind- rated DSM-III-R diagnoses, psychometric tests and DNA on 250 individuals. We have recently replicated the finding of our original study (Enoch et al 1995) in a comparable sample of subjects and have found the same result in the group of 117 unrelated individuals from the total sample, namely that there is a phenotype-phenotype association between LVA EEG and a subtype of alcoholism that is associated with anxiety disorders. LVA was the EEG phenotype of 24% of the alcoholics, 36% of those with an anxiety disorder and 75% of the alcoholics with an anxiety disorder as compared to 8% of the individuals without alcoholism or an anxiety disorder. In order to have sufficient power to map genes for alcoholism, the focus of this study has shifted to a Plains American Indian tribe which has a high prevalence of alcoholism. Thus far we have an extensive data set (psychiatric diagnoses and DNA) on 350 tribal members from large pedigrees; an EEG pilot study conducted on 69 of these individuals showed a high prevalence of the LVA phenotype. Formerly titled """"""""Genetics studies of the electroencephalogram and event-related potentials.""""""""
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