Pharmacogenomic findings from clinical whole exome sequencing of diagnostic odyssey patients

Cousin, Margot A.; Matey, Eric T.; Blackburn, Patrick R.; Boczek, Nicole J.; McAllister, Tammy M.; Kruisselbrink, Teresa M.; Babovic‐Vuksanovic, Dusica; Lazaridis, Konstantinos N.; Klee, Eric W.

doi:10.1002/mgg3.283

Cited by 26 publications

(18 citation statements)

References 44 publications

(77 reference statements)

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“…While most likely unrelated to the clinical indication for sequencing, the test results may nonetheless inform treatment decisions. [37] Furthermore, direct-to-consumer testing may provide an opportunity for patients to order testing on their own [38] and share the test results with providers.…”

Section: Overview Of Pgx Testingmentioning

confidence: 99%

Integrating pharmacogenetic testing into primary care

Haga

2017

Expert Review of Precision Medicine and Drug Development

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Introduction Pharmacogenetic (PGx) testing has greatly expanded due to enhanced understanding of the role of genes in drug response and advances in DNA-based testing technology development. As many primary care visits result in a prescription, the use of PGx testing may be particularly beneficial in this setting. However, integration of PGx testing may be limited as no uniform approach to delivery of tests has been established and providers are ill-prepared to integrate PGx testing into routine care. Areas covered In this paper, the readiness of primary care practitioners are reviewed as well as strategies to address these barriers based on published research and ongoing activities on education and implementation of PGx testing. Expert Commentary Widespread integration of PGx testing will warrant continued education and point-of-care decisional support. Primary care providers may also benefit from consultation services or team-based care with laboratory medicine specialists, pharmacists, and genetic counselors.

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Section: Overview Of Pgx Testingmentioning

confidence: 99%

Integrating pharmacogenetic testing into primary care

Haga

2017

Expert Review of Precision Medicine and Drug Development

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“…Next generation sequencing (NGS) approaches specifically designed for PGx have shown promising results, with high concordance (91–99%) with conventional PGx methods . Moreover, Cousin et al . have shown that extracting information on three PGx genes from existing clinical WES data can be beneficial in terms of drug dose and response in a small cohort of 94 patients.…”

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confidence: 99%

“…Next generation sequencing (NGS) approaches specifically designed for PGx have shown promising results, with high concordance (91-99%) with conventional PGx methods. [8][9][10] Moreover, Cousin et al 11 have shown that extracting information on three PGx genes from existing clinical WES data can be beneficial in terms of drug dose and response in a small cohort of 94 patients. However, this study is limited by investigating a small number of PGx genes rather than extracting a full panel of genes with actionable recommendations in PGx guidelines as well as by the use of a limited sample size.…”

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confidence: 99%

Repurposing of Diagnostic Whole Exome Sequencing Data of 1,583 Individuals for Clinical Pharmacogenetics

Lee

Allard

Bollen

et al. 2019

Clin Pharma and Therapeutics

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For ~ 80 drugs, widely recognized pharmacogenetics dosing guidelines are available. However, the use of these guidelines in clinical practice remains limited as only a fraction of patients is subjected to pharmacogenetic screening. We investigated the feasibility of repurposing whole exome sequencing (WES) data for a panel of 42 variants in 11 pharmacogenes to provide a pharmacogenomic profile. Existing diagnostic WES‐data from child‐parent trios totaling 1,583 individuals were used. Results were successfully extracted for 39 variants. No information could be extracted for three variants, located in CYP2C19, UGT1A1, and CYP3A5, and for CYP2D6 copy number. At least one actionable phenotype was present in 86% of the individuals. Haplotype phasing proved relevant for CYP2B6 assignments as 1.5% of the phenotypes were corrected after phasing. In conclusion, repurposing WES‐data can yield meaningful pharmacogenetic profiles for 7 of 11 important pharmacogenes, which can be used to guide drug treatment.

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“…In a series of whole exome sequencing results on 94 young patients with a median age of 10 years, a subset of PGx variants in CYP2C19, CYP2C9, and VKORC1 was reported. 3 Most tested patients had dominant neurologic pathology (71%) and were currently taking medications (90%). Of the 94 PGx-evaluated patients, 91% had at least 1 variant allele reported, and 20% had potential immediate implications on current medication use.…”

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confidence: 99%

“…Of the 94 PGx-evaluated patients, 91% had at least 1 variant allele reported, and 20% had potential immediate implications on current medication use. 3 Therefore, the decision about selecting the patient-appropriate test, with or without components such as PGx or secondary results, should take into account multiple factors, including the indication for testing and the clinical scenario.…”

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confidence: 99%