Prior GWASs have identified several top SNPs that, while not reaching genome-wide significance, associated replicably to higher opioid analgesic dose, and implicated genes CREB1, TAOK3, and TRPC3.41, 45, 46 We found that a genetic score (GS) calculated using these dose-increasing alleles was associated with higher methadone dose, and that the relationship was more evident in AAs than EAs (AA: n = 383, two-tailed P = 6.6 × 10−4; EA: n = 1,027, two-tailed P = 8.0 × 10−2; meta-analysis P = 1.3 × 10−3, Supplemental Table 5) (an explanation of how the GS was derived is provided in Supplemental Methods).
