Because of its potential functional significance, many human genetic studies of substance dependence have targeted rs1799971. However, the role, if any, of rs1799971 in substance dependence remains unclear (Crist and Berrettini 2013; Levran et al. 2012; Mague and Blendy 2010). In studies of opioid dependence, results have been mixed, with the minor (G) allele reported to have no effect in some studies (Crowley et al. 2003; Levran et al. 2008; Nelson et al. 2014; Nikolov et al. 2011) and to decrease risk in others (Bond et al. 1998; Tan et al. 2003). Similarly, analyses of alcohol dependence have reported increased risk (Bart et al. 2005; Kim et al. 2004), no effect (Bergen et al. 1997; Rouvinen-Lagerstrom et al. 2013; Sander et al. 1998; Xuei et al. 2007), and decreased risk (Schinka et al. 2002; Town et al. 1999) for this allele. Analyses of rs1799971 with other addictive substances also show no consensus (Clarke et al. 2013; Crist and Berrettini 2013; Franke et al. 2001; Gelernter et al. 1999; Hardin et al. 2009; Munafo et al. 2013).
