Figure 1:

A. In some instances, variants in single genes (often those determining pharmacokinetics, as highlighted in Figure 2) have large effect sizes, and distinct metabolizer phenotypes can be predicted: poor metabolizers with two loss of function alleles, intermediate metabolizers with one functional allele, normal metabolizers with two functional alleles, and ultrarapid metabolizers with duplications or other variants conferring increased metabolic activity. In this situation, distinct genotype-dependent differences in drug response may be seen, although there may still be overlap. B. When variants in many pharmacogenes contribution to variability in drug action, the distribution of drug responses is not polymodal as (A), but rather a continuum.