In the domain of human measured genotype studies, GWAS studies offer the prospect of novel genetic findings (albeit most probably on a more limited scale than was initially hoped). However, in the alcohol field, such studies have been designed based on the AUD phenotype, without regard to stratification by environmental exposure history. Thus, they will also have limited power to model GXE effects and use these to inform gene discovery. Despite high initial enthusiasm for the single genetic variant – single exposure approach that was illustrated in the serotonin transporter work of Caspi et al. (2003), the ultimate failure of replication attempts (Munafo et al., 2009; Risch et al), and low power of studies reporting positive findings (Munafo et al., 2009) cautions against undue confidence in the existing literature. In particular, studies based on sample sizes that are at least an order of magnitude larger than the first generation of studies (which typically had under a thousand individuals per sample) will be needed to give some confidence in findings (esp. for interactions involving rare environmental exposures). Studies in the human
