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

Yuan Ji, Jennifer M. Skierka, Joseph H. Blommel, Brenda E. Moore, Douglas L. Vancuyk, Jamie K. Bruflat, Lisa M. Peterson, Tamra L. Veldhuizen, Numrah Fadra, Sandra E. Peterson, Susan A. Lagerstedt, Laura J. Train, Linnea M. Baudhuin, Eric W Klee, Matthew J. Ferber, Suzette J Bielinski, Pedro Caraballo, Richard M Weinshilboum, John L. Black

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)438-445
Number of pages8
JournalJournal of Molecular Diagnostics
Volume18
Issue number3
DOIs
StatePublished - May 1 2016

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Cytochrome P-450 CYP2D6
Precision Medicine
Pharmacogenetics
DNA Sequence Analysis
Genes
Clinical Decision Support Systems
Workflow
Electronic Health Records
Clinical Protocols
Genotype
Guidelines
Pharmacogenomic Testing
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine

Cite this

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. / Ji, Yuan; Skierka, Jennifer M.; Blommel, Joseph H.; Moore, Brenda E.; Vancuyk, Douglas L.; Bruflat, Jamie K.; Peterson, Lisa M.; Veldhuizen, Tamra L.; Fadra, Numrah; Peterson, Sandra E.; Lagerstedt, Susan A.; Train, Laura J.; Baudhuin, Linnea M.; Klee, Eric W; Ferber, Matthew J.; Bielinski, Suzette J; Caraballo, Pedro; Weinshilboum, Richard M; Black, John L.

In: Journal of Molecular Diagnostics, Vol. 18, No. 3, 01.05.2016, p. 438-445.

Research output: Contribution to journalArticle

Ji, Y, Skierka, JM, Blommel, JH, Moore, BE, Vancuyk, DL, Bruflat, JK, Peterson, LM, Veldhuizen, TL, Fadra, N, Peterson, SE, Lagerstedt, SA, Train, LJ, Baudhuin, LM, Klee, EW, Ferber, MJ, Bielinski, SJ, Caraballo, P, Weinshilboum, RM & Black, JL 2016, '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', Journal of Molecular Diagnostics, vol. 18, no. 3, pp. 438-445. https://doi.org/10.1016/j.jmoldx.2016.01.003
Ji, Yuan ; Skierka, Jennifer M. ; Blommel, Joseph H. ; Moore, Brenda E. ; Vancuyk, Douglas L. ; Bruflat, Jamie K. ; Peterson, Lisa M. ; Veldhuizen, Tamra L. ; Fadra, Numrah ; Peterson, Sandra E. ; Lagerstedt, Susan A. ; Train, Laura J. ; Baudhuin, Linnea M. ; Klee, Eric W ; Ferber, Matthew J. ; Bielinski, Suzette J ; Caraballo, Pedro ; Weinshilboum, Richard M ; Black, John L. / 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. In: Journal of Molecular Diagnostics. 2016 ; Vol. 18, No. 3. pp. 438-445.
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