Alcohol use disorders (AUDs) represent a major public health burden. Genetic risk factors contribute critically to susceptibility to AUDs likely a result of many variants each contributing modestly to risk. Genetic studies in animal models and humans have to date made slow progress in identifying genes individual risk variants. However, modern high-throughput approaches such as genome-wide association studies or genomic expression profiling promise to rapidly increase the pool of potential candidate genes influencing AUDs. This proposal for a P50 Alcohol Research Center presents a novel and highly integrated overall design to focus on both gene discovery and functional interpretation for the genetics of AUDs. This application is the outgrowth of a P20 Developmental Center grant that established the VCU Alcohol Research Center in 2009. Having made significant progress, we propose here to extend and enlarge that Center. Our approach includes three novel features: 1) A focus on gene networks contributing to AUD-related phenotypes, rather than single genes;2) A cross-species genetic and genomics analysis to validate candidate genes and networks affecting ethanol behaviors;3) A highly integrative Center design with rapid data sharing across projects through a cross-species analysis pipeline to provide ranked gene lists or networks for further experimental validation in the component projects. We request five years of support for six research projects and pilot grants for genetic studies in mice, worms, flies, and humans. Three projects will be in human genetics with a novel clinical laboratory component for assessing targeted genetic influences on human behavioral responses to ethanol in a controlled environment. All projects will be supported by an Administrative Core, an Analytic and Informatics Core and a Rodent Behavioral Core. The scientific work proposed in these projects and cores are clearly greater than the sum of their parts, due to the highly interactive structure of the VCU-ARC components. The VCU-ARC is well positioned to become a national resource making major contributions to the advancement of our understanding of the etiology of AUDs and their prevention and treatment.
Use of genetic and genomic data across species can define gene networks mediating ethanol responses and inform candidate gene selection for development of future diagnostic or therapeutic approaches. This focus provides the VCU-ARC a novel and highly significant justification with potential for contributing broadly to the alcohol research field and to public health.
|Webb, Bradley T; Edwards, Alexis C; Wolen, Aaron R et al. (2017) Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students. Front Genet 8:30|
|Conley, A H; Overstreet, C M; Hawn, S E et al. (2017) Prevalence and predictors of sexual assault among a college sample. J Am Coll Health 65:41-49|
|Mathies, Laura D; Aliev, Fazil; COGA Investigators et al. (2017) Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations. Alcohol Clin Exp Res 41:2033-2040|
|Cooke, Megan E; Neale, Zoe E; Barr, Peter B et al. (2017) The Role of Social, Familial, and Individual-Level Factors on Multiple Alcohol Use Outcomes During the First Year of University. Alcohol Clin Exp Res 41:1783-1793|
|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|
|Spindle, Tory R; Hiler, Marzena M; Cooke, Megan E et al. (2017) Electronic cigarette use and uptake of cigarette smoking: A longitudinal examination of U.S. college students. Addict Behav 67:66-72|
|Lopez, Marcelo F; Miles, Michael F; Williams, Robert W et al. (2017) Variable effects of chronic intermittent ethanol exposure on ethanol drinking in a genetically diverse mouse cohort. Alcohol 58:73-82|
|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|
|Chartier, Karen G; Karriker-Jaffe, Katherine J; Cummings, Cory R et al. (2017) Review: Environmental influences on alcohol use: Informing research on the joint effects of genes and the environment in diverse U.S. populations. Am J Addict 26:446-460|
|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|
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