We investigated whether the implicated SNP upstream of OPRM1 also influences sensitivity to the analgesic effects of opioids. Because the observed association between rs73568641 and methadone dose was evident only in AAs, we examined the effect of rs73568641 in an independent AA sample. The only published GWAS of opioid dosage in AAs that we are aware of is our earlier study41, wherein we examined intravenous morphine dose in AA pediatric patients recovering from tonsillectomy and adenoidectomy. In these AA subjects (dose mean (SD) = 118.6 micrograms/kilogram (μg/kg) (39.8 μg/kg)), rs73568641-C was associated with a higher required morphine dose (n = 241, β = 11.6 μg/kg, standard error (SE) = 5.6 μg/kg, two-tailed P = 3.9 × 10−2), the same effect direction as for methadone dose (Figure 3). In EA patients from the CHOP sample (dose mean (SD) = 132.4 μg/kg (40.9 μg/kg)), no association between rs73568641-C and morphine dose was present (n = 277, P = 0.33). These consistent results across independent samples indicate that the effects of the locus are apparent in African-ancestry but not European-ancestry populations (no other populations were tested).
