Consistent with the Overall aims of the PARC, Core C002 will focus on robust identification of genes and gene networks involved in the etiology of ethanol use disorders by studying naturally occurring variation in voluntary ethanol preference/consumption, and will also study genetic contributions to the consequences of ethanol use. Priority for expression and sequence comparisons will be determined based on several criteria, including putative biological role and likely relevance to ethanol action. QPCR, PCR, and sequencing will be used to confirm initial co-expression and co-splicing identified in mice and non-human primate model systems, prior to experimental perturbation and validation. C002 will be active in all years of requested Center support, and will continue to focus on biostatistics and bioinformatics support, as well as continuing to provide critical expertise in sample and library preparation and initial confirmation to aid in prioritization of targets for the Validation Core C001. Core C002 plays a critical role for data integration of the diverse readouts generated by the Projects (e.g., expression, genetic variants, epigenetics, imaging, behavioral phenotypes) that is necessary in order to elucidate the underlying relevant brain circuitry and changes in the brain that are relevant to genetic risk for alcohol use as well as the consequences of use. This Core will facilitate hypothesis-driven (candidate gene) and hypothesis-generating (network) analyses to address the Center goals. In some cases an underlying candidate gene may be the same in animal models (mice or nonhuman primates) and humans and will be prioritized for further study. In other cases, animal model research may identify a gene network relevant in humans, with a hub that could be manipulated to examine network effects. Analyses of both candidate genes and networks will be more powerful than either alone to provide the interlocking levels of proof to move from gene/network to mechanism, and better prevent and treat alcohol abuse/dependence by identifying new risk factors associated with chronic alcohol abuse use.
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