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An interesting brief communication by Kennedy and colleagues appeared in the Genomic Medicine journal from Nature in February 2024.
Study starting points
The study evaluated the concordance of pharmacogenomic (PGx) diplotype calls between a commercial targeted genotyping panel and whole-genome sequencing (WGS). The study cohort encompassed individuals with cardiac disease from diverse racial and ethnic backgrounds. The study’s starting point was the recognition of the under-representation of diverse populations in commercial PGx panels. Such shortcomings may lead to misassignments of metabolizer status and exacerbate health disparities. The study aimed to address this gap in representation and improve pharmacotherapy guidance for all patients.
Key findings
- Whole genome sequencing (WGS) identified rare variants in 1% of the cohort that altered the interpretation of metabolizer status, potentially preventing errors in gene-based dosing.
- Commercial pharmacogenetic testing panels capture only a fraction of the genetic variation underlying medication metabolism and predisposition to adverse reactions.
- Rare variants account for roughly 30–40% of functional pharmacogenetic variation, highlighting the importance of comprehensive testing methods.
- The study emphasizes the need for increased inclusivity and global representation in pharmacogenetic testing to ensure that testing captures the full spectrum of genetic variation across diverse populations.
- The use of WGS for pharmacogenetic testing provides a more comprehensive assessment of genetic variation in pharmacogenes compared to targeted commercial panels.
Implications for Future Pharmacogenetic Practices:
- Inclusive Genetic Testing: There’s a pressing need for pharmacogenetic testing panels to include a broader spectrum of genetic variants to cater to global population diversity.
- Policy and Practice Updates: The findings advocate for updates in clinical guidelines to incorporate newly recognized variants that affect drug metabolism, especially those pertinent to underrepresented populations.
- Advancing Personalized Medicine: The study underscores the importance of using advanced genomic technologies like WGS to refine drug therapy, moving towards more personalized and effective healthcare solutions.
Conclusion
The study concludes that WGS should be integrated into routine pharmacogenetic testing. This may overcome the limitations of current commercial genotyping panels, which often fail to represent the genetic diversity of global populations. Highlighting significant disparities in detecting key pharmacogenetic variants, especially among non-European groups, the research demonstrates how these shortcomings can lead to ineffective or unsafe medication prescriptions. The study calls for urgent updates to pharmacogenetic testing panels and clinical guidelines to include a broader spectrum of genetic variants, ensuring that personalized medicine benefits all individuals equitably. By embracing the advancements in genomic technologies like WGS, healthcare can move towards genuinely personalized and inclusive treatment protocols, improving outcomes across diverse populations.
