Standardizing <i><scp>CYP</scp>2D6</i> Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group

TLDR

CYP2D6 genotype‑to‑phenotype translation varies across laboratories and guidelines, leading to inconsistent therapeutic recommendations. A modified‑Delphi process involving 37 international experts through calls and surveys produced a uniform translation system. Consensus was achieved (>70%) with 82% agreement, and widespread adoption by CPIC, DPWG, and laboratories is expected to standardize CYP2D6 interpretation.

Abstract

Translating CYP 2D6 genotype to metabolizer phenotype is not standardized across clinical laboratories offering pharmacogenetic (PGx) testing and PGx clinical practice guidelines, such as the Clinical Pharmacogenetics Implementation Consortium ( CPIC ) and the Dutch Pharmacogenetics Working Group ( DPWG ). The genotype to phenotype translation discordance between laboratories and guidelines can cause discordant cytochrome P450 2D6 (CYP2D6) phenotype assignments and, thus lead to inconsistent therapeutic recommendations and confusion among patients and clinicians. A modified‐Delphi method was used to obtain consensus for a uniform system for translating CYP 2D6 genotype to phenotype among a panel of international CYP 2D6 experts. Experts with diverse involvement in CYP 2D6 interpretation (clinicians, researchers, genetic testing laboratorians, and PGx implementers; n = 37) participated in conference calls and surveys. After completion of 7 surveys, a consensus (&gt; 70%) was reached with 82% of the CYP 2D6 experts agreeing to the final CYP 2D6 genotype to phenotype translation method. Broad adoption of the proposed CYP 2D6 genotype to phenotype translation method by guideline developers, such as CPIC and DPWG , and clinical laboratories as well as researchers will result in more consistent interpretation of CYP2D6 genotype.