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Lee, M. van der; Allard, W.G.; Bollen, S.; Santen, G.W.E.; Ruivenkamp, C.A.L.; Hoffer, M.J.V.; ... ; Swen, J.J. (2019)

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

Article / Letter to editor
For similar to 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...Show moreFor similar to 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.Show less
All authors
Lee, M. van der; Allard, W.G.; Bollen, S.; Santen, G.W.E.; Ruivenkamp, C.A.L.; Hoffer, M.J.V.; Kriek, M.; Guchelaar, H.J.; Anvar, S.Y.; Swen, J.J.
Date
2019-11-21
Journal
Clinical Pharmacology and Therapeutics
DOI
doi:10.1002/cpt.1665