A. Gaedigk and S. Leeder together with PharmGKB published an
article in
Genetics in Medicine about the prediction of CYP2D6 phenotypes from
genotype data across world populations (http://www.nature.com/gim/journal/vaop/ncurrent/full/gim201680a.html).
In the supplemental materials of Clinical Pharmacogenetics
Implementation Consortium (CPIC) guidelines involving CYP2D6 (https://www.pharmgkb.org/view/dosing-guidelines.do?source=CPIC and https://cpicpgx.org/guidelines/), allele
frequencies across populations have been systematically captured and updated
with each new guideline or update. Using this frequency table, the article
describes the calculation of diplotype frequencies and the translation
into phenotype based on the activity score system. The prevalence of
genetically predicted poor, intermediate, normal, and ultrarapid metabolizer
phenotypes are presented for major populations.
The
article also includes a critical discussion highlighting the challenges of
phenotype prediction from genotype data. This includes the overestimation of
certain alleles in studies with minimal CYP2D6 genotyping and issues of
grouping alleles and resulting diplotypes into functional and phenotype
categories.
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