Requirements for Comprehensive Pharmacogenetic Genotyping Platforms

Abstract

Recent research highlighted the large extent of rare variants in pharmacogenes and, on this basis, it was estimated that rare variants account for 30–40% of the functional variability in pharmacogenes. It has been proposed that comprehensive next-generation sequencing (NGS)-based sequencing of pharmacogenes could soon be a cost-effective methodology for clinical routine genotyping. Yet, multiple challenges on technical, interpretative and ethical levels need to be overcome to enable the reasonable dissemination of comprehensive pharmacogenetic genotyping, that includes rare genetic variation, into clinical practice. We argue that current pre-emptive pharmacogenetic testing cannot be based on comprehensive approaches but needs to be restricted to validated variants. Rather, comprehensive strategies should only be used for retrospective analyses of patients exhibiting unanticipated drug responses. Thereby, subsequent to computational analyses and functional validations, emerging variants with confirmed functional relevance can be incorporated into candidate genotyping strategies, thus refining and enhancing future pre-emptive genetic testing.

Keywords::

• clinical implementation
• genetic variation
• personalized medicine
• pharmacogenomics
• precision medicine

Financial & competing interests disclosure

The research in the laboratory is financed by The Swedish Research Council and by EU/IMI. VM Lauschke was supported by a MarieCurie IEF fellowship for career development in the context of the European FP7 framework program. VM Lauschke and M Ingelman-Sundberg are founders and owners of HepaPredict AB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The research in the laboratory is financed by The Swedish Research Council and by EU/IMI. VM Lauschke was supported by a MarieCurie IEF fellowship for career development in the context of the European FP7 framework program. VM Lauschke and M Ingelman-Sundberg are founders and owners of HepaPredict AB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.