Alcohol dependence (AD) is a complex, highly heritable disorder characterized by compulsive, excessive consumption of alcohol, resulting in physical, psychological and social impairment (American Psychiatric Association 1994) that constitutes a significant health and economic burden in the US (Harwood 2000), with 4–5% of the population affected at any given time (Li et al. 2007). Family, twin and adoption studies have consistently shown a substantial genetic contribution to disease etiology (Goodwin et al. 1974; McGue 1999; Nurnberger et al. 2004), with heritability estimates ranging from 50–80% (Heath et al. 1997; Knopik et al. 2004). To date a number of genes have been implicated in alcoholism susceptibility via linkage analysis, candidate gene approaches and genome-wide association studies (GWAS), including the often replicated GABRA2 (Edenberg et al. 2004; Bierut et al. 2010) and ADH4 (Guindalini et al. 2005; Luo et al. 2004; Edenberg et al. 2006), among others (Wang et al. 2004; Xuei et al. 2006; Chen et al. 2009; Zlojutro et al. 2011; Bierut et al. 2012). However, these genetic loci collectively account for only a small fraction of the risk of AD, with effects varying across ethnic groups (Gelernter & Kranzler 2009).
