title: Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans.
abstract: 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).
authors.affiliation: Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: W
authors.initials: W
authors.lastname: Hernandez
authors.affiliation: Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Gamazon
authors.affiliation: Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Aquino-Michaels
authors.affiliation: Department of Pharmacy, University of Illinois, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington DC, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: O'Brien
authors.affiliation: 1] Department of Pharmacology and Physiology, The George Washington University, Washington DC, USA [2] Department of Pharmacogenomics, Bernard J. Dunn School of Pharmacy, Shenandoah University, Ashburn, VA, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Harralson
authors.affiliation: Department of Medicine, Institute of Human Genetics, University of Illinois, Chicago, IL, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Kittles
authors.affiliation: Department of Medicine, The George Washington University, Washington DC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Barbour
authors.affiliation: Department of Veterans Affairs, Uniformed Services University of the Health Sciences, Washington DC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tuck
authors.affiliation: 1] Department of Medicine, The George Washington University, Washington DC, USA [2] Department of Veterans Affairs, Uniformed Services University of the Health Sciences, Washington DC, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: McIntosh
authors.affiliation: Department of Veterans Affairs, Uniformed Services University of the Health Sciences, Washington DC, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Douglas
authors.affiliation: Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Nicolae
authors.affiliation: Department of Pharmacy, University of Illinois, Chicago, IL, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Cavallari
authors.affiliation: Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Perera
mesh_terms: D000925:Anticoagulants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
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