African-Americans and European-Americans. Important information could be provided by understanding how coding and non-coding variations interact in determining the ADH1B function and how ADH1B regulatory mechanisms are shared with the other ADH genes. Investigating ADH1B molecular pathways, we observed that this gene is involved in metabolism of multiple drugs, including ifosfamide, cyclophosphamide, abacavir, and celecoxib (PharmGKB data). To our knowledge, no study has investigated the effect of the known ADH1B functional alleles on the pharmacokinetics/pharmacodynamics of these drugs. Future studies should also deepen our understanding of ADH1B functions not related to alcohol metabolism. Our recent PheWAS highlighted that ADH1B rs1229984 is associated with a wide range of phenotypic traits and some of these appear not to be mediated by alcohol use [Polimanti and others 2016a]. Additional support regarding non-alcohol-related functions of ADH1B is provided by evolutionary studies. The strong selection signatures observed in the ADH1B locus in Asian populations (with suggestive evidence of convergent evolution in Europeans; [Galinsky and others 2016]) are very likely not related to alcohol consumption, mainly because ALDH2, the other locus affecting alcohol drinking behaviors in Asians (and with an even stronger effect), does not show any genomic selection signature. Both our PheWAS and the evolutionary
