To integrate the case and control genetic studies, a meta-analysis was completed including 22 articles and over 8,000 individuals across multiple drugs of abuse (primarily alcohol and opioid dependence) (Arias et al., 2006). This meta-analysis failed to support an association between the Asn40Asp SNP and substance dependence. These results were not moderated by substance of abuse (i.e., alcohol vs. opioid) or study population (Arias et al., 2006). This meta-analysis, as well as previous population studies (Gelernter et al., 1999), also highlighted the allele frequency imbalance for this polymorphism across population groups. The estimated minor allele (Asp40) frequency is 3 to 16% in Caucasians, 0 to 5% in African Americans, and 25 to 47% in Asian populations. Ethnicity effects were also found in a very recent study of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin-dependent individuals, such that African Americans displayed a lower degree of methylation between cases and controls (Nielsen et al., 2010). Taken together, at this time, the results of association studies do not support the Asn40Asp SNP as a risk factor for alcoholism and
