Chunk #11 — Results — Methadone dose genome-wide association study (GWAS) in the Yale-Penn OD sample identifies a significant association upstream of OPRM1 at rs73568641
Table 1 provides an overview of the GWAS sample demographics. Dose data for AAs (mean (standard deviation (SD)) = 68.0 mg (30.1 mg)) and EAs (mean (SD) = 77.8 mg (33.9 mg)) are shown in Supplemental Figures 1 and 2, respectively. Summary statistics for all SNPs with P < 5.0 × 10−5 in AAs are provided in Supplemental Table 1, and summary statistics for all SNPs with P < 5.0 × 10−5 in EAs are provided in Supplemental Table 2. The GWAS conducted in AAs identified one genome-wide significant region on chromosome 6 (lead SNP rs73568641, n = 383, P = 2.8 × 10−8, Supplemental Table 3; AA quantile-quantile (QQ) plot is shown in Supplemental Figure 3). Lead SNP rs73568641 tags an association peak approximately ~300 kilobases (kb) upstream of the OPRM1 transcription start site (Figure 1). Rs73568641 genotypes did not deviate from Hardy-Weinberg equilibrium expectiations.43 In AAs, the minor (C) allele of rs73568641 (MAF = 0.1) was associated with a higher daily methadone dose: TT genotype (n = 310), dose mean (SD) = 64.4 mg (29.8 mg); TC genotype
