Recent advances in genetics, particularly large scale genome‐wide association studies (GWAS), including several by the Collaborative Study on the Genetics of Alcoholism (COGA; see 4. Genetics in this issue) have identified loci associated with complex genetic disorders, including alcohol use disorders (AUD) 1 , 2 , 3 , 4 , 5 and other Substance Use Disorders (SUD). 6 , 7 While larger sample sizes have led to the identification of more loci and strengthened the confidence in putative loci, progress toward understanding the molecular mechanisms underlying AUD risk has been challenging. 8 The loci identified by GWAS as associated with increased risk for AUD or other SUD are often large and contain many genes and variants in linkage disequilibrium (LD; groups of variants within a locus are frequently inherited with each other). In some cases, the most significant variant(s) in a locus may not be the one(s) that contribute to risk for the trait. In addition, many of the variants are in noncoding regions, suggesting that gene regulation is a key mechanism. A major challenge to the field has been elucidating which variants and genes actually contribute to the risk for AUD. 8
