Although family, twin, and adoption studies have convincingly demonstrated that genetic actors play an important role in the etiology of Alcohol Dependence (AD), the specific genomic location of genes that influence the susceptibility to AD in man remains largely unknown. While the probability of detection Of susceptibility genes for complex traits like AD is uncertain, current evidence suggests that the probability of success can be enhanced by adopting such methods as the use of selected and systematically ascertained samples of large size obtained from a population with substantial genetic and cultural homogeneity.In this application, we propose to carry out a study employing such methods. We hope to ascertain, from population-based registers in 3 counties in Ireland, 1,700 siblings from 800 multiplex sibships who meet narrow DSM-IV based criteria for AD. All siblings so ascertained will be systematically evaluated by trained mental health professionals using a personal interview that covers a detailed lifetime history for alcohol use, abuse and dependence and assesses such other risk factors as the lifetime history of psychiatric disorders (e.g. major depression, antisocial personality), the history of non-alcohol substance abuse/dependence, personality, childhood symptoms of conduct disorder and hyperactivity, and response to and attitudes towards alcohol. Personal interviews will be supplemented by information obtained from hospital records and from family informants. DNA will be sampled from all cooperative siblings and parents. This application requests support solely for data collection and """"""""phenotypic"""""""" data analysis. If it is funded, we will follow up with a request for funds to support the genotyping and linkage analysis of the data we obtain. Power simulations indicate that this sample will, under most realistic conditions, have adequate power to detect individual genes with only a modest impact on the susceptibility to AD. Phenotypic analyses of the data will focus on detecting familial resemblance for symptoms, factors and typologies of AD to be used to define putative etiologic subtypes of AD for future linkage analyses.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA011408-05
Application #
6371414
Study Section
Clinical and Treatment Subcommittee (ALCP)
Project Start
1997-09-25
Project End
2002-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
5
Fiscal Year
2001
Total Cost
$218,060
Indirect Cost
Name
Virginia Commonwealth University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Savage, Jeanne E; Salvatore, Jessica E; Aliev, Fazil et al. (2018) Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples. Alcohol Clin Exp Res 42:520-530
Adkins, Amy E; Hack, Laura M; Bigdeli, Tim B et al. (2017) Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms. Alcohol Clin Exp Res 41:911-928
Verhulst, B; Neale, M C; Kendler, K S (2015) The heritability of alcohol use disorders: a meta-analysis of twin and adoption studies. Psychol Med 45:1061-72
Salvatore, J E; Prom-Wormley, E; Prescott, C A et al. (2015) Overlapping genetic and environmental influences among men's alcohol consumption and problems, romantic quality and social support. Psychol Med 45:2353-64
Edwards, Alexis C; Maes, Hermine H; Prescott, Carol A et al. (2015) Multiple mechanisms influencing the relationship between alcohol consumption and peer alcohol use. Alcohol Clin Exp Res 39:324-32
Kendler, Kenneth S; Edwards, Alexis C; Gardner, Charles O (2015) Sex differences in the pathways to symptoms of alcohol use disorder: a study of opposite-sex twin pairs. Alcohol Clin Exp Res 39:998-1007
Wichers, Marieke; Gillespie, Nathan A; Kendler, Kenneth S (2013) Genetic and environmental predictors of latent trajectories of alcohol use from adolescence to adulthood: a male twin study. Alcohol Clin Exp Res 37:498-506
Kendler, Kenneth S; Aggen, Steven H; Patrick, Christopher J (2013) Familial influences on conduct disorder reflect 2 genetic factors and 1 shared environmental factor. JAMA Psychiatry 70:78-86
Kendler, K S (2013) Decision making in the pathway from genes to psychiatric and substance use disorders. Mol Psychiatry 18:640-5
Crabbe, John C; Kendler, Kenneth S; Hitzemann, Robert J (2013) Modeling the diagnostic criteria for alcohol dependence with genetic animal models. Curr Top Behav Neurosci 13:187-221

Showing the most recent 10 out of 53 publications