APPLICANT S ABSTRACT: The objective of the proposed research is to identify genes involved in the etiology of alcohol dependence. The research will utilize a set of already collected families of alcoholics, including 250 sib pairs. These families were ascertained through male and female affected sib pairs and include at least one parent from each nuclear family. DNA and in-person diagnostic information are available for all of these individuals. The existence of this valuable resource will enable us to conduct a two-stage genome scan for the purpose of localizing alcoholism susceptibility genes, utilizing state-of-the-art automated genotyping. In the first stage, we will utilize markers spaced at approximately IO cM intervals to detect linkages greater than 1.5. These """"""""hot spots"""""""" will be followed up with genotyping of multiple flanking markers at more densely spaced intervals (2 cM). In view of the significant resource which our sample represents, the proposed work has a potential for uncovering significant linkages between specific chromosomal regions and our alcoholism phenotype. The combined resources of our research team will situate us to initiate positional cloning of a gene, should significant positive linkages be found with our Stage I and Stage 11 genotyping endeavors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA011304-03
Application #
2894171
Study Section
Clinical and Treatment Subcommittee (ALCP)
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Hill, Shirley Y; O'Brien, Jessica (2015) Psychological and Neurobiological Precursors of Alcohol Use Disorders in High Risk Youth. Curr Addict Rep 2:104-113
Hill, Shirley Y; Jones, Bobby L; Zezza, Nicholas et al. (2013) Family-based association analysis of alcohol dependence implicates KIAA0040 on Chromosome 1q in multiplex alcohol dependence families. Open J Genet 3:243-252
Hill, Shirley Y; Jones, Bobby L; Holmes, Brian et al. (2013) Cholinergic receptor gene (CHRM2) variation and familial loading for alcohol dependence predict childhood developmental trajectories of P300. Psychiatry Res 209:504-11
Hill, Shirley Y; Terwilliger, Robert; McDermott, Michael (2013) White matter microstructure, alcohol exposure, and familial risk for alcohol dependence. Psychiatry Res 212:43-53
Hill, Shirley Y; Weeks, Daniel E; Jones, Bobby L et al. (2012) ASTN1 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families. Am J Med Genet B Neuropsychiatr Genet 159B:445-55
Hill, Shirley Y (2010) Neural plasticity, human genetics, and risk for alcohol dependence. Int Rev Neurobiol 91:53-94
Hill, Shirley Y; Shen, Sa; Locke Wellman, Jeannette et al. (2005) Offspring from families at high risk for alcohol dependence: increased body mass index in association with prenatal exposure to cigarettes but not alcohol. Psychiatry Res 135:203-16
Hill, Shirley Y (2004) Trajectories of alcohol use and electrophysiological and morphological indices of brain development: distinguishing causes from consequences. Ann N Y Acad Sci 1021:245-59
Hill, Shirley Y; Shen, Sa; Zezza, Nicholas et al. (2004) A genome wide search for alcoholism susceptibility genes. Am J Med Genet B Neuropsychiatr Genet 128B:102-13
Hill, S Y; Shen, S; Locke, J et al. (1999) Developmental delay in P300 production in children at high risk for developing alcohol-related disorders. Biol Psychiatry 46:970-81

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