Prediction of CYP2D6 phenotype from genotype across world populations

Genet Med. 2017 Jan;19(1):69-76. doi: 10.1038/gim.2016.80. Epub 2016 Jul 7.


Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Cytochrome P-450 CYP2D6 / genetics*
  • Ethnicity / genetics
  • Female
  • Gene Frequency
  • Genetics, Population*
  • Genotype
  • Humans
  • Inactivation, Metabolic / genetics*
  • Male
  • Pharmacogenetics*
  • Phenotype
  • Polymorphism, Genetic


  • Cytochrome P-450 CYP2D6