CYP2D6 genotyping

CYP2D6 genotyping was performed at four external laboratories, and different panels were used across the studies (see Table 1). Six of the studies (N = 570) used genotyping assays allowing detection of at least the following allele variants: CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*10, and CYP2D6*41. Some studies also tested for CYP2D6*9, CYP2D6*16, CYP2D6*17, and/or CYP2D6*29. The wild‐type allele (CYP2D6*1) was assigned when no variant alleles were identified. Five of the studies (N = 546) tested for gene duplication (denoted “XN”), but none of the assays provided information on which allele was duplicated or the actual number of gene copies.

CYP2D6 genotypes were translated into an activity score and predicted CYP2D6 phenotype according to the consensus guideline from the CPIC and DPWG.2 For heterozygous duplicated genotypes where the two alleles had different functionalities (e.g., *1/*4XN or *1/*10XN), no activity score was assigned.

An overview of the CYP2D6 genotypes identified along with their associated activity scores and predicted phenotypes is provided in Table S1.