Accurate CYP2D6 genotyping using whole genome sequencing data

Responsible for the metabolism of 25% of all drugs, CYP2D6 is a critical component of personalized medicine initiatives. Genotyping CYP2D6 is challenging due to sequence similarity with its pseudogene paralog CYP2D7 and a high number and variety of common structural variants (SVs). Here we describe a software tool, Cyrius, that accurately genotypes CYP2D6 using whole-genome sequencing. We show that Cyrius has superior performance (96.5% concordance with truth genotypes) compared to existing methods (83.8-86.6%). Using Cyrius, we built a haplotype frequency database from 2504 ethnically diverse samples and estimate that SV-containing star alleles are more frequent than previously reported.