The challenges and goals for the next phase of genetic research on alcohol dependence (AD) will be to i) confirm candidate genes, ii) to understand the mechanism(s) of action for individual genes in AD and iii) to use the molecular and genetic information to identify potential targets for novel interventions in AD. As a strategy to approach these complex goals, we have formulated three major organizing hypotheses that integrate and direct the individual components of this Developmental (P20) application. These include: 1. A focus on gene networks rather than individual genes which will provide mechanistic information, target identification and cross-species validation of molecular events affecting alcohol-related behaviors and risk for AD. 2. A bi-directional cross-species gene discovery and validation scheme that can provide both powerful confirmation of candidate genes and mechanistic information. Our planned studies in mice (Project 1), humans (Project 2, Pilot 2), C. elegans (Project 3), and D. melanogaster (Pilot 1) will be mutually reinforcing. 3. Initial sensitivity and acute tolerance to ethanol are phenotypes with broad cross-species experimental applicability and validated relevance to AD. For this project, for which we request four years of support, we outline a series of three developmental and two pilot projects which form a highly integrated and novel approach that implement the hypotheses outlined above. An Administrative Core and Bioinformatics Core will provide needed support across projects.
The Specific Aims of individual projects will include developmental aspects that seek to broaden our scientific base, increase integration between Center components and extend our experimental models to eventually include additional behavioral phenotypes such as acute and chronic tolerance and dependence. We expect novel contributions to the field of alcohol research from our cross-species analysis of acute ethanol effects.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-BB (80))
Program Officer
Reilly, Matthew
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Virginia Commonwealth University
Schools of Medicine
United States
Zip Code
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
Amstadter, Ananda B; Myers, John M; Kendler, Kenneth S (2014) Psychiatric resilience: longitudinal twin study. Br J Psychiatry 205:275-80
Kendler, K S; Myers, J (2014) The boundaries of the internalizing and externalizing genetic spectra in men and women. Psychol Med 44:647-55
Kendler, Kenneth S; Gardner, Charles O; Hickman, Matt et al. (2014) Socioeconomic status and alcohol-related behaviors in mid- to late adolescence in the Avon Longitudinal Study of Parents and Children. J Stud Alcohol Drugs 75:541-5
Salvatore, Jessica E; Kendler, Kenneth S; Dick, Danielle M (2014) Romantic relationship status and alcohol use and problems across the first year of college. J Stud Alcohol Drugs 75:580-9
Muldoon, P P; Jackson, K J; Perez, E et al. (2014) The ?3?4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies. Br J Pharmacol 171:3845-57
Chan, Robin F; Lewellyn, Lara; DeLoyht, Jacqueline M et al. (2014) Contrasting influences of Drosophila white/mini-white on ethanol sensitivity in two different behavioral assays. Alcohol Clin Exp Res 38:1582-93
Ystrom, Eivind; Reichborn-Kjennerud, Ted; Neale, Michael C et al. (2014) Genetic and environmental risk factors for illicit substance use and use disorders: Joint analysis of self and co-twin ratings. Behav Genet 44:1-13
Vanderlinden, Lauren A; Saba, Laura M; Kechris, Katerina et al. (2013) Whole brain and brain regional coexpression network interactions associated with predisposition to alcohol consumption. PLoS One 8:e68878
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

Showing the most recent 10 out of 34 publications