In our hypothesis-driven association study of heroin addiction, two OPRM1 intron 1 variants (#6, #8) were found at a significantly higher frequency in subjects with heroin addiction than in healthy controls, suggesting an association with heroin addiction.9 A 10K genome-wide association study from our laboratory that used a subset of the sample population, used in the hypothesis-driven study, indicated association of a SNP rs1074287 (#4) in the 5′ flanking region (−11.6 kb from exon 1) with heroin addiction.32 Analysis of the HapMap CEU LD data in this study revealed a unique haplogroup (“INT1”) of 42 SNPs that spans intron 1 and also includes at least four variants in the 20 kb 5′ flanking region, including rs1074287. This data indicate that the finding of the two studies are compatible and refer to the same “IVS1” haplogroup. Based on this data, the intron 1 SNPs that show association with heroin addiction may be markers in high LD with regulatory variants in the proximal 5′ region. It is also possible that the SNPs in the 5′ flanking region are markers for functional SNPs in intron 1.
