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 identified 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 strongly heritable, traitlike, 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 247 individuals. We have recently replicated the association of LVA with a subtype of alcoholism with anxiety in a comparable sample of 149 unrelated individuals (Enoch et al 1999). LVA was found in 23% of alcoholics, 25% of subjects with an anxiety disorder and 56% of alcoholics with an anxiety disorder compared to 8% of the individuals without alcoholism or an anxiety disorder. In order to obtain 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. During the course of this year we performed EEGs and ERPs on 374 tribal members from large pedigrees. We have almost completed the data set of psychiatric diagnoses and DNA from these individuals.We will soon be in a position to start analyses for mapping genes for alcoholism.Formerly titled Genetic studies of the electroencephalogram and event-related potentials. - health & behavior, neurosciences, drinking patterns & causes, electrophysiology/EEG, molecular genetics - Human Subjects: Interview, Questionaires, or Surveys Only

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000280-10
Application #
6288661
Study Section
Special Emphasis Panel (LNG)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Jung, Y; Goldman, D (2018) Role of RNA modifications in brain and behavior. Genes Brain Behav 17:e12444
Reilly, Matthew T; Noronha, Antonio; Goldman, David et al. (2017) Genetic studies of alcohol dependence in the context of the addiction cycle. Neuropharmacology 122:3-21
Goldman, David (2014) The missing heritability of behavior: the search continues. Psychophysiology 51:1327-8
Zhou, Zhifeng; Enoch, Mary-Anne; Goldman, David (2014) Gene expression in the addicted brain. Int Rev Neurobiol 116:251-73
Ho, M K; Goldman, D; Heinz, A et al. (2010) Breaking barriers in the genomics and pharmacogenetics of drug addiction. Clin Pharmacol Ther 88:779-91
Araya, Ricardo; Hu, Xianzhang; Heron, Jon et al. (2009) Effects of stressful life events, maternal depression and 5-HTTLPR genotype on emotional symptoms in pre-adolescent children. Am J Med Genet B Neuropsychiatr Genet 150B:670-82
Enoch, Mary-Anne; White, Kenneth V; Waheed, Juwaria et al. (2008) Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders. Depress Anxiety 25:383-92
Reuter, Martin; Jeste, Neelum; Klein, Thomas et al. (2007) Association of THR105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), with alcoholism in German Caucasians. Drug Alcohol Depend 87:69-75
Enoch, Mary-Anne; Shen, Pei-Hong; Xu, Ke et al. (2006) Using ancestry-informative markers to define populations and detect population stratification. J Psychopharmacol 20:19-26
Enoch, Mary-Anne; Waheed, Juwaria F; Harris, Claudia R et al. (2006) Sex differences in the influence of COMT Val158Met on alcoholism and smoking in plains American Indians. Alcohol Clin Exp Res 30:399-406

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