Variant Discovery Using Next-Generation Sequencing and its Future Role in Pharmacogenetics

Abstract

Next-generation sequencing (NGS) has enabled the discovery of a multitude of novel and mostly rare variants in pharmacogenes that may alter a patient’s therapeutic response to drugs. In addition to single nucleotide variants, structural variation affecting the number of copies of whole genes or parts of genes can be detected. While current guidelines concerning clinical implementation mostly act upon well-documented, common single nucleotide variants to guide dosing or drug selection, in silico and large-scale functional assessment of rare variant effects on protein function are at the forefront of pharmacogenetic research to facilitate their clinical integration. Here, we discuss the role of NGS in variant discovery, paving the way for more comprehensive genotype-guided pharmacotherapy that can translate to improved clinical care.

Keywords::

• adverse drug events
• next-generation sequencing
• pharmacogenetics
• precision medicine
• rare variation

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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