To provide functional support for GWAS candidates, we tested whether perturbation of orthologous genes alters behavioral response to ethanol in C. elegans and/or Drosophila, depending on the presence of orthologous genes and the availability of genetic reagents and information. In vertebrate MO, we analyzed correlations between candidate gene expression and alcohol phenotypes bioinformatically in curated archival data from recombinant inbred mouse lines and we tested the effect of pharmacological antagonism of one candidate gene product on motivation to self-administer ethanol in rats after chronic ethanol exposure. For one candidate gene with no ortholog outside of primates, we tested for expression differences in alcohol dependent and control human post-mortem brain tissue stratified by clinical status or genotype.
