Using binary alcohol dependence diagnoses (affected/unaffected) in genetic studies necessarily ignores information about the clinical and etiological heterogeneity of alcohol dependence. With growing recognition that clinical diagnoses are likely to be far removed from the genetic underpinnings, there has been increasing effort to perform genetic analyses in human samples using alternative phenotypes that may more closely reflect the biological basis of the disorder. In the field of alcohol research, more recent human association studies have branched out beyond clinical diagnoses and analyzed a number of different, more focused phenotypes related to alcohol use, for example, alcohol consumption patterns, craving, and physiological response to alcohol. However, most of this work has been conducted in a largely nonsystematic, exploratory manner, with little justification for the inclusion or exclusion of particular phenotypes across studies. This pilot project will conduct a systematic analysis of the alcohol dependence phenotype, and related aspects of alcohol use, to parse the phenotype into genetically informed components for use in genetic association analyses. Data from the Virginia Twin Study will be used, in which >9250 adult twins were assessed with comprehensive psychiatric interviews, to conduct multivariate analyses examining the genetic architecture across alcohol dependence criteria, measures of alcohol use/drinking patterns, and comorbid psychiatric disorders. In the same way that factor analysis provides information about the underlying phenotypic factor structure, the use of genetically informative twin data provides information about the underlying genetic factor structure across the variables. The emergent factor structure from the twin analyses can then be used to create genetic factor scores for subjects in the Irish Alcohol Dependence Study (Project 2) for use as secondary phenotypes in genetic association tests, to compare with results from dependence diagnoses and model organisms. Accordingly, this pilot aims to be a first step toward tackling the inherent phenotypic complexity associated with alcohol use and dependence and related traits. Of particular relevance to the VCU-ARC, we hypothesize that expanding the phenotypes analyzed in human studies will provide greater congruence with results from model organism studies where alcohol-related traits, rather than alcohol diagnoses per se, are modeled.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory Grants (P20)
Project #
1P20AA017828-01
Application #
7929389
Study Section
Special Emphasis Panel (ZAA1-BB (80))
Project Start
2009-09-25
Project End
2011-08-31
Budget Start
2009-09-25
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$34,019
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Bourdon, Jessica L; Moore, Ashlee A; Long, Elizabeth C et al. (2018) The relationship between on-campus service utilization and common mental health concerns in undergraduate college students. Psychol Serv :
van der Vaart, Andrew; Meng, Xianfang; Bowers, M Scott et al. (2018) Glycogen synthase kinase 3 beta regulates ethanol consumption and is a risk factor for alcohol dependence. Neuropsychopharmacology 43:2521-2531
Su, Jinni; Kuo, Sally I-Chun; Meyers, Jacquelyn L et al. (2018) Examining interactions between genetic risk for alcohol problems, peer deviance, and interpersonal traumatic events on trajectories of alcohol use disorder symptoms among African American college students. Dev Psychopathol 30:1749-1761
Edwards, Alexis C; Deak, Joseph D; Gizer, Ian R et al. (2018) Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity. Alcohol Clin Exp Res 42:2349-2359
Tubbs, Justin D; Savage, Jeanne E; Adkins, Amy E et al. (2018) Mindfulness moderates the relation between trauma and anxiety symptoms in college students. J Am Coll Health :1-11
Do, Elizabeth K; Prom-Wormley, Elizabeth C; Fuemmeler, Bernard F et al. (2018) Associations Between Initial Subjective Experiences with Tobacco and Self-Reported Recent Use in Young Adulthood. Subst Use Misuse 53:2291-2298
Peterson, Roseann E; Edwards, Alexis C; Bacanu, Silviu-Alin et al. (2017) The utility of empirically assigning ancestry groups in cross-population genetic studies of addiction. Am J Addict 26:494-501
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
van der Vaart, Andrew D; Wolstenholme, Jennifer T; Smith, Maren L et al. (2017) The allostatic impact of chronic ethanol on gene expression: A genetic analysis of chronic intermittent ethanol treatment in the BXD cohort. Alcohol 58:93-106
Bono, Rose S; Barnes, Andrew J; Dick, Danielle M et al. (2017) Drinking, Cigarette Smoking, and Employment Among American College Freshmen at a Four-Year University. Subst Use Misuse 52:182-193

Showing the most recent 10 out of 93 publications