Fig. 1.

a Association between the tramadol to O-desmethyltramadol ratio (T:M1) for individual genotypes at UGT2B7, ABCB1, OPRM1, and COMT. A dashed horizontal line indicates the threshold for significance after correction for multiple testing (−log₁₀(p_adj) = 5.62); loci are labeled if they exceed the significance threshold and have regression coefficients ≥ 0.45 (arbitrarily selected to avoid locus label overlap). b Heritability summary of restricted maximum likelihood (--reml in Genome-wide Complex Trait Analysis) analyses, with the first 20 eigenvectors as covariates, of the toxicologically inferred metabolizer phenotype (t-MP; solid gray triangles) and the associated t-MP (T:M1; solid black circles) phenotypes. A dashed horizontal line indicates the threshold for significance after correction for multiple testing (−log₁₀(p_adj) = 2.79); two data points are labeled, indicating that the individual (UGT2B7) and combined (CYP2D6/UGT2B7) genotype information significantly explained a relatively high proportion of phenotypic variance