Development of an Ancestrally Inclusive Preemptive Pharmacogenetic Testing Panel

Area of Science:

• Pharmacogenomics
• Clinical Chemistry
• Molecular Diagnostics

Background:

• Current pharmacogenetic (PGx) testing often lacks diversity and is expensive, limiting access for underserved communities.
• Personalized pharmacotherapy relies on understanding individual genetic variations influencing drug response.
• Preemptive PGx testing can optimize drug selection and dosing, improving patient outcomes.

Purpose of the Study:

• To develop and validate GatorPGx Plus, a cost-effective, preemptive PGx panel.
• To ensure inclusivity for diverse patient populations by selecting variants with significant allele frequencies across ancestries.
• To assess the clinical utility and cost-effectiveness of the developed PGx panel.

Main Methods:

• Selection of pharmacogenes and variants based on clinical impact, guideline recommendations, and allele frequencies (approx. ≥1%) in major ancestral populations.
• Development of a high-throughput, cost-efficient assay with automated reporting, including a CYP2D6 copy number assay.
• Validation of the panel for accuracy, precision, and analytical sensitivity, followed by application to 124 participants in a clinical implementation trial.

Main Results:

• The GatorPGx Plus panel demonstrated 100% concordance with reference methods.
• The average turnaround time was 14.3 days; 99% of participants exhibited at least one non-normal function phenotype.
• CYP2C19 (69.4%) showed the most frequent non-normal function phenotypes, with certain CYP2D6 and CYP2C19 variants found at higher frequencies than in European populations.

Conclusions:

• GatorPGx Plus is a clinically validated, low-cost, preemptive PGx panel suitable for diverse populations.
• The panel effectively captures clinically relevant variants in mixed-ancestry individuals.
• This cost-effective approach has significant potential for improving pharmacogenetic implementation in medically underserved communities.