Potential of whole-genome sequencing-based pharmacogenetic profiling

Pharmacogenomics. 2021 Feb;22(3):177-190. doi: 10.2217/pgs-2020-0155. Epub 2021 Feb 1.


Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been performed using targeted genotyping that focuses on common/known variants. Recently, whole-genome sequencing (WGS) is emerging as a more comprehensive short-read next-generation sequencing approach, enabling both gene diagnostics and pharmacogenetic profiling, including rare/novel variants, in a single assay. Using the example of the pharmacogene CYP2D6, we demonstrate the potential of WGS-based pharmacogenetic profiling as well as emphasize the limitations of short-read next-generation sequencing. In the near future, we envision a shift toward long-read sequencing as the predominant method for gene diagnostics and pharmacogenetic profiling, providing unprecedented data quality and improving patient care.

Keywords: CYP2D6; adverse drug reactions; long-read sequencing; next-generation sequencing; pharmacogenetics; precision medicine; pseudogenes; structural variation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gene Expression Profiling / methods*
  • Gene Expression Profiling / trends
  • High-Throughput Nucleotide Sequencing / methods
  • High-Throughput Nucleotide Sequencing / trends
  • Humans
  • Pharmacogenetics / methods
  • Pharmacogenetics / trends
  • Pharmacogenomic Testing / methods*
  • Pharmacogenomic Testing / trends
  • Precision Medicine / methods*
  • Precision Medicine / trends
  • Whole Genome Sequencing / methods*
  • Whole Genome Sequencing / trends