Human laboratory models have increasingly evaluated genetic correlates of subjective, neural and behavioral responses to alcohol (e.g., Kareken et al., 2010; Ramchandani et al., 2011; Ray and Hutchison, 2007). These studies reflect an “intermediate phenotype” approach that prioritizes laboratory-based measures over diagnostic outcomes, given expectations for improved phenotype precision and closer correspondence with neurobiological processes (Enoch et al., 2003; Hines et al., 2005). In the context of alcohol addiction, the advantages of this approach are illustrated by recent work implicating variation in the μ-opioid receptor gene (OPRM1) as relevant for individual variation in responses to alcohol. Most studies have focused on a common polymorphism (A118G, rs1799971) in exon 1 of the gene (Heilig et al., 2011; Mague and Blendy, 2010; Ray et al., 2012a). Notably, initial human laboratory studies found that participants with the minor (G) allele reported greater hedonic responses to alcohol (Ray and Hutchison, 2004, 2007), greater cue-elicited craving (van den Wildenberg et al., 2007), and enhanced mesolimbic activation during exposure to alcohol cues (Filbey et al., 2008) relative to participants homozygous for the common (A) allele.
