The long-term objective of the research proposed here is to identify the genetic and environmental contributions to individual differences in alcohol consumption and subsequent alcohol-related problems. This quantitative behavioral genetic proposal includes a prospective study of """"""""normal"""""""" alcohol users who are asked annually to complete questionnaire information about their alcohol consumption, life events in the past year, and alcohol-related symptoms or problems. Subjects include 58 pairs on non-twin siblings, 48 pairs of fraternal twins, 57 pairs of identical twins, and 54 pairs of biologically unrelated (adoptive) siblings. All have previously completed individual Il-hour laboratory tests within the CARTA (Colorado Alcohol Research on Twins and Adoptees) project here of physiological, psychomotor, and cognitive functions, and assessments of mood, 3 times while sober and 3 times while BAC was held near 100 mg/dl. From these pre-and post-alcohol measurements, alcohol sensitivity and acute tolerance scores have been computed for each person on each function. The original (1983-87) CARTA design outlined a plan for individual testing of about 100 persons/year for 5 years, and subsequent assessment of alcohol consumption and alcohol-related problems via annual questionnaire. To date, all laboratory measures are complete, and questionnaire data have been collected on schedule (83-86% return rate). For renewal funding, CARTA proposed extensions to hormonal and biochemical measurements of extreme groups (e.g., high vs low sensitive; high vs low consumers) of former subjects, with annual mailing costs included in the budget. This renewal proposal was criticized by the review group for our inability to match subjects adequately, and was not supported. Questionnaire costs for the past year have been paid via a supplemental award to CARTA for this purpose. This proposal requests funds for continuation of this previously approved prospective study of this valuable, genetically and environmentally informative group of subjects. Via maximum likelihood quantitative genetic techniques, including cross-covariance studies of pair members on different measures, we will be able to identify the genetic contribution to the phenotypic association between, e.g., earlier measures such as Sensitivity (from CARTA) and later measures, such as consumption or specific alcohol-related problems. This powerful design allows estimation of both the heritability and the coefficient of environmental determination for each trait, as well as estimation of the genetic and common environmental contributions to the association between traits or measures--even across years.
| Bardag-Gorce, Fawzia; Dedes, Jennifer; French, Barbara A et al. (2007) Mallory body formation is associated with epigenetic phenotypic change in hepatocytes in vivo. Exp Mol Pathol 83:160-8 |
| Rodriguez, L A; Wilson, J R; Nagoshi, C T (1993) Does psychomotor sensitivity to alcohol predict subsequent alcohol use? Alcohol Clin Exp Res 17:155-61 |
| Rhea, S A; Nagoshi, C T; Wilson, J R (1993) Reliability of sibling reports on parental drinking behaviors. J Stud Alcohol 54:80-4 |
| Nagoshi, C T; Wilson, J R; Rodriguez, L A (1991) Impulsivity, sensation seeking, and behavioral and emotional responses to alcohol. Alcohol Clin Exp Res 15:661-7 |
