animal and human studies were summarized and various candidate genes involved were implicated in influencing level of response to alcohol.15 These include genes related to the second-messenger system (adenylyl cyclase [AC]/cyclic adenosine-3′,5′-monophosphate [cAMP] system), neurotransmitters (endogenous opioids, serotonin, γ-aminobutyric acid [GABA], adenosine, dopamine), and alcohol metabolism (alcohol dehydrogenase, catalase, cytochrome P450 enzyme CYP 2E1). For example, a recent study by Ray and Hutchison28 has found an association between the A118G single nucleotide polymorphism (SNP) of the μ-opioid receptor gene and sensitivity to the effects of alcohol. Specifically, individuals with at least one copy of the G allele, which codes for the more potent μ-opioid receptors, displayed higher sensitivity to the stimulatory, sedative, mood-altering, and subjective feelings of intoxication.28 Furthermore, previous studies have implicated a polymorphism in the promoter region of the serotonin transporter gene (5′HTLPR, locus ID SLC6A4) with subjective feelings of intoxication during an alcohol challenge protocol using a nonclinical sample.29 Taken together, these studies underscore the importance of evaluating individual differences in alcohol sensitivity, particularly with regard to the quality of the alcohol intoxication, as a potential endophenotype for alcohol use disorders. Some of the strengths of this endophenotype include its specificity, state-independence, heritability, and biological and clinical
