Elucidating the functional consequences of genetic variants and how they contribute to disease risk is critical for understanding neuropsychiatric diseases such as AUD. Animal models, particularly in rodents, have been widely implemented to investigate genetic findings from human studies, but they have several key limitations. While rodent models of psychiatric disease provide important behavioral insight, they typically focus on manipulating a single gene, and often fail to recapitulate the full scope of molecular and cellular phenotypes. This is perhaps best illustrated by the plethora of Alzheimer’s disease rodent models, none of which demonstrates combination of plaques, tangles, and neurodegeneration found in human post-mortem tissue (Elder et al., 2010), unless mutant genes are expressed in combination, a condition not found in humans (Oddo et al., 2003). The lack of adequate animal models hampers clinical studies, with many potential therapies failing in early phase clinical trials (Becker and Greig, 2010). In the context of AUD, animal models typically focus on consumption phenotypes (Lynch et al., 2010). However, recent genetic data suggest that the shared heritability for consumption (Bierut et al., 2012; Clarke
