Alcohol Research Center

Project 4 of the VCU Alcohol Research Center uses human data to accomplish three complementary goals: (1) advance discovery of genes involved in alcohol-related outcomes using multivariate genomic techniques, (2) characterize the risk associated with identified variants in diverse longitudinal samples to understand the pathways of risk associated with identified variants, across development, and in conjunction with the environment, and (3) create synergistic connections between model organism and human studies to advance our understanding of how genetic influences impact alcohol-related outcomes. Each of these areas represent critical steps in using genetic data to improve prevention, intervention, and treatment for alcohol use disorders (AUDs); results from the previous cycle have already been used to successfully fund a spin-off project that involves building a tailored prevention program incorporating genetic and environmental risk information. The next phase of Project 4 is a direct extension of the successful strategy used in the previous cycle, expanded to include new samples and statistical techniques to further advance discovery. The aims of Project 4 are to (Aim 1) apply multivariate genomic methods to capitalize on genetic sharing between alcohol use phenotypes and other psychiatric and behavioral traits to boost power to detect common variants associated with alcohol use outcomes, and to characterize the pathways by which genetic variants operate. Bioinformatic characterization of these identified genetic variant results through the Data Analysis, Integration and Resource Sharing (DAIRS) Component, and in collaboration with Project 5, will help elucidate underlying biological risk pathways. We will then apply results from these multivariate analyses to five complementary longitudinal datasets, consisting of both population-based and high-risk samples, in order to (Aim 2a): map the behavioral phenotypes associated with the genetic risk scores identified in Aim 1 from adolescence to mid-life; (Aim 2b) test for pathways of risk specific to sex and racial/ethnic background; and (Aim 2c) integrate genetic with environmental risk information to improve clinical prediction. Finally, Aim 3 establishes a bidirectional pipeline for translation of human and model organism results, creating prioritized gene lists for further interrogation by the model organism projects, and conducting gene- and locus-based tests for genes and systems emerging from model organism projects in our longitudinal phenotype datasets, to characterize the human behavioral outcomes associated with implicated genes. This will allow us to better understand the effect of these genes in the human system and on the alcohol outcomes that are ultimately of interest.