Consequences of CYP2D6 Copy-Number Variation for Pharmacogenomics in Psychiatry

Abstract

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Pharmacogenomics represents a potentially powerful enhancement to the current standard of care for psychiatric patients. However, a variety of biological and technical challenges must be addressed in order to provide adequate clinical decision support for personalized prescribing and dosing based on genomic data. This is particularly true in the case of CYP2D6, a key drug-metabolizing gene, which not only harbors multiple genetic variants known to affect enzyme function but also shows a broad range of copy-number and hybrid alleles in various patient populations. Here, we describe several challenges in the accurate measurement and interpretation of data from the CYP2D6 locus including the clinical consequences of increased copy number. We discuss best practices for overcoming these challenges and then explore various current and future applications of pharmacogenomic analysis of CYP2D6 in psychiatry.

Keywords

• personalized medicine
• precision medicine
• gene deletion
• gene duplications
• pharmacogenomics
• cytochrome P450 CYP2D6