title: The population attributable fraction as a measure of the impact of warfarin pharmacogenetic testing.
abstract: OBJECTIVE
  We aimed to estimate the population impact of warfarin pharmacogenetic testing (WPGT) across multiple populations.
  
  
  METHODS
  We used the expanded International Warfarin Pharmacogenetics Consortium data set and genotype frequencies from HapMap to simulate dose distributions for each CYP2C9/VKORC1 genotype combination in the different races, and calculated the population attributable fraction as a measure of population impact of WPGT. WPGT was compared to both clinical and fixed-dose algorithms to estimate the benefits of WPGT.
  
  
  RESULTS
  Our dose simulation revealed different dose requirements in difference races and considerable overlap in dose distributions of different genotype combinations. Population attributable fraction calculations suggest that complete implementation of WPGT can reduce inaccurate dosing by 18-24% in white individuals. However black, Japanese and Chinese patients do not benefit from WPGT, especially when compared against a race-specific fixed dose.
  
  
  CONCLUSIONS
  Our findings support WPGT in white individuals but not in black, Japanese and Chinese individuals.
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Sze Ling
authors.initials: SL
authors.lastname: Chan
authors.forename: Chen
authors.initials: C
authors.lastname: Suo
authors.forename: Kee Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Yik Ying
authors.initials: YY
authors.lastname: Teo
mesh_terms: D001741:Black or African American / Q000235:genetics; D000925:Anticoagulants / Q000008:administration & dosage; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D001777:Blood Coagulation / Q000187:drug effects; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005828:Genetics, Population; D005838:Genotype; D060148:HapMap Project; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*; D044465:White People / Q000235:genetics
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases