Preemptive Pharmacogenomic Testing for Precision Medicine: A Comprehensive Analysis of Five Actionable Pharmacogenomic Genes Using Next-Generation DNA Sequencing and a Customized CYP2D6 Genotyping Cascade

J Mol Diagn. 2016 May;18(3):438-445. doi: 10.1016/j.jmoldx.2016.01.003. Epub 2016 Mar 3.


Significant barriers, such as lack of professional guidelines, specialized training for interpretation of pharmacogenomics (PGx) data, and insufficient evidence to support clinical utility, prevent preemptive PGx testing from being widely clinically implemented. The current study, as a pilot project for the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment Protocol, was designed to evaluate the impact of preemptive PGx and to optimize the workflow in the clinic setting. We used an 84-gene next-generation sequencing panel that included SLCO1B1, CYP2C19, CYP2C9, and VKORC1 together with a custom-designed CYP2D6 testing cascade to genotype the 1013 subjects in laboratories approved by the Clinical Laboratory Improvement Act. Actionable PGx variants were placed in patient's electronic medical records where integrated clinical decision support rules alert providers when a relevant medication is ordered. The fraction of this cohort carrying actionable PGx variant(s) in individual genes ranged from 30% (SLCO1B1) to 79% (CYP2D6). When considering all five genes together, 99% of the subjects carried an actionable PGx variant(s) in at least one gene. Our study provides evidence in favor of preemptive PGx testing by identifying the risk of a variant being present in the population we studied.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 CYP2C19 / metabolism
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Enzyme Activation
  • Gene Duplication
  • Genotype*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Pharmacogenetics / methods*
  • Phenotype
  • Precision Medicine / methods*


  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6