A small number of the 51 iMO–human-AUD genes (Table 4) have well-established roles in 1 or more features of AUD. Human ADH1A, ADH1B, ADH1C, ALDH2, ALD-DH18A1, and ALDH4A1, genes that encode key alcohol-metabolizing enzymes, are associated with alcohol dependence, alcohol intake, and other related phenotypes in numerous human studies (Table 4). The human genes CHRNA3, DRD1, GAD1, NPY, and SLC18A2 have also been implicated in AUD by multiple studies in humans (Table 4). Given that these human genes are the most or among the most widely accepted for having roles in AUD, it is noteworthy that the invertebrate orthologs of all of these genes influence behavioral responses to acute alcohol exposure (Tables 1 and 2). The remaining 40 iMO–human-AUD genes have been implicated in human AUD by smaller scale or single studies (Table 4). Although it is not clear at this time whether these 40 genes have bona fide roles in human AUD given the lack of replication of the associations in independent populations, the results from studies on the invertebrate orthologs of these genes suggest that additional human studies are warranted.
