TY - JOUR
T1 - Low-cost generation of clinical-grade, layperson-friendly pharmacogenetic passports using oligonucleotide arrays
AU - Lifelines NEXT cohort study
AU - Lanting, Pauline
AU - Warmerdam, Robert
AU - Slager, Jelle
AU - Brugge, Harm
AU - Ochi, Taichi
AU - Benjamins, Marloes
AU - Lopera-Maya, Esteban
AU - Jankipersadsing, Soesma
AU - Gelderloos-Arends, Jody
AU - Teuben, Daphne
AU - Hendriksen, Dennis
AU - Charbon, Bart
AU - Johansson, Lennart
AU - Munnink, Thijs Oude
AU - de Boer-Veger, Nienke
AU - Wilffert, Bob
AU - Swertz, Morris
AU - Touw, Daan
AU - Deelen, Patrick
AU - Knoers, Nine
AU - Dekens, Jackie
AU - Franke, Lude
N1 - Copyright © 2025 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
PY - 2025/4/1
Y1 - 2025/4/1
N2 - Pharmacogenomic (PGx) information is essential for precision medicine, enabling drug prescriptions to be personalized according to an individual's genetic background. Almost all individuals will carry a genetic marker that affects their drug response, so the ideal drug prescription for these individuals will differ from the population-level guidelines. Currently, PGx information is often not available at first prescription, reducing its effectiveness. In the Netherlands, pharmacogenetic information is most often obtained using dedicated single-gene assays, making it expensive and time consuming to generate complete multi-gene PGx profiles. We therefore hypothesized that we could also use genome-wide oligonucleotide genotyping arrays to generate comprehensive PGx information (PGx passports), thereby decreasing the cost and time required for PGx testing and lowering the barrier to generating PGx information prior to first prescription. Taking advantage of existing genetic data generated in two biobanks, we developed and validated Asterix, a low-cost, clinical-grade PGx passport pipeline for 12 PGx genes. In these biobanks, we performed and clinically validated genetic variant calling and statistical phasing and imputation. In addition, we developed and validated a CYP2D6 copy-number-variant-calling tool, forgoing the need to use separate PCR-based copy-number detection. Ultimately, we returned 1,227 PGx passports to biobank participants via a layperson-friendly app, improving knowledge of PGx among citizens. Our study demonstrates the feasibility of a low-cost, clinical-grade PGx passport pipeline that could be readily implemented in clinical settings to enhance personalized healthcare, ensuring that patients receive the most effective and safe drug therapy based on their unique genetic makeup.
AB - Pharmacogenomic (PGx) information is essential for precision medicine, enabling drug prescriptions to be personalized according to an individual's genetic background. Almost all individuals will carry a genetic marker that affects their drug response, so the ideal drug prescription for these individuals will differ from the population-level guidelines. Currently, PGx information is often not available at first prescription, reducing its effectiveness. In the Netherlands, pharmacogenetic information is most often obtained using dedicated single-gene assays, making it expensive and time consuming to generate complete multi-gene PGx profiles. We therefore hypothesized that we could also use genome-wide oligonucleotide genotyping arrays to generate comprehensive PGx information (PGx passports), thereby decreasing the cost and time required for PGx testing and lowering the barrier to generating PGx information prior to first prescription. Taking advantage of existing genetic data generated in two biobanks, we developed and validated Asterix, a low-cost, clinical-grade PGx passport pipeline for 12 PGx genes. In these biobanks, we performed and clinically validated genetic variant calling and statistical phasing and imputation. In addition, we developed and validated a CYP2D6 copy-number-variant-calling tool, forgoing the need to use separate PCR-based copy-number detection. Ultimately, we returned 1,227 PGx passports to biobank participants via a layperson-friendly app, improving knowledge of PGx among citizens. Our study demonstrates the feasibility of a low-cost, clinical-grade PGx passport pipeline that could be readily implemented in clinical settings to enhance personalized healthcare, ensuring that patients receive the most effective and safe drug therapy based on their unique genetic makeup.
KW - pharmacogenetics
KW - pharmacogenomics
KW - PGx profile
KW - PGx passport
KW - clinical pharmacogenomics
KW - layperson communication
KW - oligonucleotide array
U2 - 10.1016/j.ajhg.2025.03.003
DO - 10.1016/j.ajhg.2025.03.003
M3 - Article
C2 - 40174590
SN - 0002-9297
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
ER -