Development of an Ancestrally Inclusive Preemptive Pharmacogenetic Testing Panel

Abstract

Pharmacogenetic (PGx) testing can individualize pharmacotherapy, but many current panels lack inclusivity for diverse populations and are often cost-prohibitive for medically underserved communities. This study aimed to develop and validate GatorPGx Plus, a low-cost, preemptive PGx panel tailored for diverse patient populations. Pharmacogenes were selected based on the drug/drug classes potentially influenced by their variants, the clinical severity of drug-gene interactions, or the strength of guideline recommendations or emerging evidence. Variants within the pharmacogenes were included if their allele frequencies were approximately 1% or greater in any major ancestral population. The panel was validated for accuracy, precision, and analytical sensitivity and applied to 124 participants from an ongoing pharmacogenetic clinical implementation trial. To reduce costs, a high-throughput platform was chosen, laboratory technician hands-on time was minimized, and result translation and reporting were automated. The panel comprised tests for 62 variants in 14 genes/gene regions, including a CYP2D6 copy number assay. It demonstrated 100% concordance with reference methods. The average turnaround time between test order and results was 14.3 (±6.4) days. Among the 124 genotyped trial participants (mean age 60 years, 57.3% female), 99% had at least one non-normal function (less common or higher-risk) phenotype. The most frequently identified non-normal function phenotypes were in CYP2C19 (69.4%). CYP2D6 *17, *29, and CYP2C19 *9 were captured at higher frequencies than reported in European populations. GatorPGx Plus is a low per-test cost, clinically validated, preemptive PGx panel that effectively captures key variants in a mixed-ancestry population, underscoring its potential clinical utility in diverse, medically underserved populations.

Keywords: ancestrally inclusive; panel; pharmacogenetics; preemptive.