The large number of genes identified in iMO studies (Tables 1 and 2) highlight the power of the fly and worm model systems for investigating fundamental molecular-genetic mechanisms that influence behavioral responses to alcohol. The utility of the iMOs for identifying orthologs of individual genes or conserved genetic pathways involved in human AUD, however, has not been systematically evaluated. In fact, as counterpoints to the conservation in behavioral responses to alcohol and the molecular underpinnings of nervous system function in humans and iMOs discussed above, there are a number of notable differences between studies in invertebrates and humans that could, in principle, lead to disparate findings across species. For example, studies in humans examine naturally occurring genetic variation that has undergone natural selection during evolution and (typically) determine how that variation is associated with problems related to chronic alcohol exposure that often lasts for years. Studies in iMOs are often just the opposite. Genetic variance in iMOs is usually generated in the laboratory, although naturally occurring genetic variation in EtOH responsiveness in worms and flies has been assessed in some
