While no receptors are dedicated specifically to alcohol, this drug has prominent effects on gamma aminobutyric acid (GABA), glutamate, opioid, dopamine, serotonin (5-HT), and acetylcholine systems and on the hypothalamic-pituitary axis (HPA), each of which could contribute to alcohol sensitivity (Koob and Volkow, 2010). Each effect relates to sets of genes and environmental forces, and, thus, evaluations of gene × gene (G × G) and gene × environment (G × E) interactions are important in understanding how genes relate to how a person responds to alcohol (Goldman, 2010). Few gene effects are likely to follow Mendelian patterns; some gene variants are rare across families, but common within relatives (Choquet et al., 2013); and most are relatively common but explain small proportions of sensitivity phenomena (Joslyn et al., 2010, 2011; Manolio et al., 2009; McCarthy and Hirschorn, 2008; Wang et al., 2005).
