of influence conferred by rs1799971 (Arias et al., 2006; Chen et al., 2012; Schwantes-An et al., 2016). Most recently, the largest of these investigations assessed both general substance dependence (as defined by a DSM-IV lifetime dependence diagnosis for any of five substances: alcohol, nicotine, cannabis, cocaine, and opioids), as well as the individual substance dependence diagnoses in European ancestry individuals. Findings demonstrated a protective relation between the rs1799971-G allele and the general substance dependence phenotype, and this allele showed a similar direction of effect but was not significantly associated with specific dependence diagnosis (Schwantes-An et al., 2016), potentially due to a lack of power. Although this meta-analysis provides promising insight into the role of rs1799971 in substance use more generally, rather than alcohol specifically, the longstanding interest in and theoretical underpinnings of the role of the endogenous opioid system in subjective response to alcohol warrants further research to elucidate the influence of genetic variation within OPRM1.
