Variants that do not alter the amino acid sequence can also be relevant to gene function, possibly by affecting gene expression. Hancock et al. identified 16 polymorphisms within OPRM1 that were associated with the expression levels of OPRM1 transcript in the prefrontal cortex [18]. One variant, rs3778150, was significantly associated with opioid dependence in a mixed population of African- and European-Americans (case n = 2004, control n = 8753). The effect of rs3778150 was replicated in an independent population of European descent (case n = 1976, control n = 3144), whereas the effect was the same direction but not significant in a much smaller African-American replication sample (case n = 307, control n = 545). The study also described an interaction between rs3778150 and rs1799971; rs1799971 was only associated with opioid dependence in the presence of the C allele of rs3778150. These results suggest a possibility that disparate findings for rs1799971 across different populations may be partially due to differences in relevant genetic background.
