Studies have already begun to use GWAS results to inform our understanding of etiological mechanisms, such as the existence of genetic heterogeneity and subtypes within disease classifications (e.g. Edwards et al., 2016; Traylor et al., 2012), and biological pathways that cross diagnostic boundaries, with genetic risk shared across disorders (Cross Disorder Working Group of the PGC, 2013; Bulik-Sullivan et al., 2015; Andersen et al., 2017). For alcohol phenotypes, investigations of GWAS-identified variants have begun to disentangle which genes directly impact alcohol use (e.g. alcohol metabolism genes) and which have indirect effects through a broader liability towards polysubstance use (Haller et al., 2014) or sensation-seeking tendencies (Aliev et al., 2015; Ashenhurst et al., 2016). For example, preliminary studies suggest that genes such as GABRA2 and aggregate polygenic risk scores may impact AUDs by influencing one’s subjective response to alcohol (Uhart et al., 2013), functional differences in brain reward systems (Heitzeg et al., 2014), and personality traits like impulsivity (Villafuerte et al., 2013; Li et al., 2017). Functional annotation of the genetic and biological processes implicated by GWAS variants (Clark et al.,
