Fig. 3
From: Integrating rare genetic variants into pharmacogenetic drug response predictions
The relevance of rare genetic variants for warfarin response and simvastatin-related myotoxicity. a Scheme depicting the metabolism and therapeutic action of warfarin. The less potent R-enantiomer of warfarin is metabolized by CYP1A1, CYP1A2, CYP3A, and CYP2C19, whereas the more potent S-enantiomer is inactivated by CYP2C9. Warfarin inhibits the VKOR complex, which reduces vitamin K, an essential factor for the formation of functional coagulation factors. See www.pharmgkb.org/pathway/PA145011113 and www.pharmgkb.org/pathway/PA145011114 for further information. b Overview of the aggregated frequencies of common (MAF ≥ 1%, blue) and rare deleterious genetic variants (MAF < 1%, red) in genes involved in warfarin pharmacokinetics or pharmacodynamics. Values next to the columns indicate the relative contribution of rare genetic variants. c Stacked column plot showing the aggregated frequency of deleterious rare variants of potential relevance for warfarin action. d Scheme depicting metabolites and genetic factors involved in the hepatic uptake, metabolism, and excretion of simvastatin. See www.pharmgkb.org/pathway/PA145011109 for further information. e Overview of the aggregated frequencies of common (MAF ≥ 1%, blue) and rare deleterious genetic variants (MAF < 1%, red) in genes implicated in simvastatin ADME. Values next to the columns indicate the relative contribution of rare genetic variants. f Stacked column plot showing the aggregated frequency of deleterious rare variants of potential relevance for simvastatin pharmacokinetics