FIG. 1.

Example of a genotype–phenotype association for a monogenic phenotype. Histograms and cluster analysis present the CYP2D6 activity (phenotype), as measured with dextromethorphan as a probe drug. CYP2D6 activity is expressed as the log of the urinary metabolic ratio of dextromethorphan/dextrorphan log(DM/DX). The red lines in A indicate the four population clusters identified by mclust, the blue line represents the summary line. Mean log(DM/DX) are as indicated for each cluster (arrows). Population histograms are shown for all subjects (B), Caucasians (C) and African Americans (D), respectively. Subjects with discordant genotypes were excluded. The mean log(DM/DX) was −1.912 for all subjects, −1.989 for Caucasians and −1.800 for African-Americans. The gray box highlights the activity range for intermediate metabolizers (−1.52288 ≤ log(DM/DX) < −0.52288 or 0.03 ≤ DM/DX < 0.3). Reprinted by permission from Macmillan Publishers Ltd: [Gaedigk et al., Clin Pharmacol Ther 2008; 83, 234–242].