A larger study by Zhang et al. [12] examined 1063 European Americans, including 620 cases diagnosed with alcohol, cocaine, and opioid dependence, and 443 control subjects without any substance use disorders [12]. The only SNP that survived multiple testing was the G80T (rs1042114) variant in exon 1 of the OPRD1 gene, which showed significantly increased frequency of the minor G allele in opioid dependent subjects (21.0%) compared to controls (13.2%, P=0.005), and a higher frequency of the rs1042114 heterozygote in opioid dependent cases (32.4%) compared to controls (24.2%, P=0.008) [12]. Haplotype analysis showed an association between six OPRD1 SNPs that contained the GCAACT sequence (including rs1042114 and rs2234918) and greater risk of opioid dependence (χ2 = 20.68, d.f. = 1, P < 0.001) [12].
