Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans

Pharmacogenomics J. 2014 Jun;14(3):223-8. doi: 10.1038/tpj.2013.34. Epub 2013 Sep 10.


Using a derivation cohort (N=349), we developed the first warfarin dosing algorithm that includes recently discovered polymorphisms in VKORC1 and CYP2C9 associated with warfarin dose requirement in African Americans (AAs). We tested our novel algorithm in an independent cohort of 129 AAs and compared the dose prediction to the International Warfarin Pharmacogenetics Consortium (IWPC) dosing algorithms. Our algorithm explains more of the phenotypic variation (R(2)=0.27) than the IWPC pharmacogenomics (R(2)=0.15) or clinical (R(2)=0.16) algorithms. Among high-dose patients, our algorithm predicted a higher proportion of patients within 20% of stable warfarin dose (45% vs 29% and 2% in the IWPC pharmacogenomics and clinical algorithms, respectively). In contrast to our novel algorithm, a significant inverse correlation between predicted dose and percent West African ancestry was observed for the IWPC pharmacogenomics algorithm among patients requiring ⩾60 mg per week (β=-2.04, P=0.02).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Anticoagulants / pharmacokinetics
  • Anticoagulants / therapeutic use*
  • Cohort Studies
  • Cytochrome P-450 CYP2C9 / genetics
  • Female
  • Humans
  • Male
  • Pharmacogenetics*
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin / pharmacokinetics
  • Warfarin / therapeutic use*


  • Anticoagulants
  • Warfarin
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases