A call for increased inclusivity and global representation in pharmacogenetic testing

Area of Science:

• Pharmacogenomics
• Genetics
• Cardiology

Background:

• Commercial pharmacogenetic testing panels incompletely capture genetic variations.
• Medication metabolism and adverse drug reactions are influenced by genetic factors.
• Understanding genetic variations is crucial for personalized medicine.

Purpose of the Study:

• To compare whole genome sequencing (WGS) with commercial panels for detecting pharmacogenetic variations.
• To assess the impact of WGS-identified variants on metabolizer status interpretation.
• To evaluate the potential for preventing gene-based dosing errors in individuals with a family history of pediatric heart disease.

Main Methods:

• Whole genome sequencing (WGS) was performed on 308 individuals.
• Detected genetic variations in six pharmacogenes were compared to a commercial testing panel.
• Analysis focused on rare variants and their effect on drug metabolism interpretation.

Main Results:

• WGS identified genetic variations not detected by commercial panels.
• In 1% of the cohort, WGS revealed rare variants that changed the interpretation of drug metabolizer status.
• These findings highlight potential inaccuracies in current commercial testing.

Conclusions:

• Whole genome sequencing provides a more thorough assessment of pharmacogenetic variation compared to commercial panels.
• WGS can identify critical rare variants that impact medication dosing and safety.
• Integrating WGS into clinical practice may improve the accuracy of pharmacogenetic testing and prevent adverse drug events.