Thus, the firsts methodologies used for identifying genes for AUD, namely, genome-wide linkage and candidate gene association studies (Agrawal and Bierut, 2012; Enoch, 2013; Rietschel and Treutlein, 2013) were moderately successful. As a whole these studies explain only a small portion of the genetic variance, because the frequency of the identified variants in these studies are usually rare in the general population and thus cannot explain the entire population variance in AUD. However, the most replicable finding from these initial studies was the identification of genetic variation in the alcohol metabolizing genes and protective effects on risk for AUD in Asian, American Indian, European, and African American populations (Bierut et al., 2012; Chen et al., 1999; Edenberg, 2007; Thomasson et al., 1991). There are several major limitations of linkage and candidate gene association studies that likely contributed to the largely unsuccessful identification of the many genes for AUD. Genetic linkage studies are conducted using large extended families across multiple generations derived from at least one affected family member. Assembling extended pedigrees required for linkage studies is labor intensive and more
