title: Prediction of CYP2D6 phenotype from genotype across world populations.
abstract: Owing to its highly polymorphic nature and major contribution to the metabolism and bioactivation of numerous clinically used drugs, CYP2D6 is one of the most extensively studied drug-metabolizing enzymes and pharmacogenes. CYP2D6 alleles confer no, decreased, normal, or increased activity and cause a wide range of activity among individuals and between populations. However, there is no standard approach to translate diplotypes into predicted phenotype.
  
  
  
  We exploited CYP2D6 allele-frequency data that have been compiled for Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (>60,000 subjects, 173 reports) in order to estimate genotype-predicted phenotype status across major world populations based on activity score (AS) assignments.
  
  
  
  Allele frequencies vary considerably across the major ethnic groups predicting poor metabolizer status (AS = 0) between 0.4 and 5.4% across world populations. The prevalence of genotypic intermediate (AS = 0.5) and normal (AS = 1, 1.5, or 2) metabolizers ranges between 0.4 and 11% and between 67 and 90%, respectively. Finally, 1 to 21% of subjects (AS >2) are predicted to have ultrarapid metabolizer status.
  
  
  
  This comprehensive study summarizes allele frequencies, diplotypes, and predicted phenotype across major populations, providing a rich data resource for clinicians and researchers. Challenges of phenotype prediction from genotype data are highlighted and discussed.Genet Med 19 1, 69-76.
authors.affiliation: Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy-Kansas City, Kansas City, Missouri, USA.|School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA.
authors.forename: Andrea
authors.identifier: 0000-0001-6968-1893
authors.initials: A
authors.lastname: Gaedigk
authors.affiliation: Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Katrin
authors.initials: K
authors.lastname: Sangkuhl
authors.affiliation: Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Whirl-Carrillo
authors.affiliation: Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Teri
authors.identifier: 0000-0001-5527-6475
authors.initials: T
authors.lastname: Klein
authors.affiliation: Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy-Kansas City, Kansas City, Missouri, USA.|School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA.
authors.forename: J Steven
authors.identifier: 0000-0001-6688-0504
authors.initials: JS
authors.lastname: Leeder
mesh_terms: D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008297:Male; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D019389:Cytochrome P-450 CYP2D6