The Role of Next-Generation Sequencing in Pharmacogenetics and Pharmacogenomics

Cold Spring Harb Perspect Med. 2019 Feb 1;9(2):a033027. doi: 10.1101/cshperspect.a033027.


Inherited genetic variations in pharmacogenetic loci are widely acknowledged as important determinants of phenotypic differences in drug response, and may be actionable in the clinic. However, recent studies suggest that a considerable number of novel rare variants in pharmacogenes likely contribute to a still unexplained fraction of the observed interindividual variability. Next-generation sequencing (NGS) represents a rapid, relatively inexpensive, large-scale DNA sequencing technology with potential relevance as a comprehensive pharmacogenetic genotyping platform to identify genetic variation related to drug therapy. However, many obstacles remain before the clinical use of NGS-based test results, including technical challenges, functional interpretation, and strict requirements for diagnostic tests. Advanced computational analyses, high-throughput screening methodologies, and generation of shared resources with cell-based and clinical information will facilitate the integration of NGS data into candidate genotyping approaches, likely enhancing future drug phenotype predictions in patients.

Publication types

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

MeSH terms

  • Computational Biology
  • Genetic Variation
  • High-Throughput Nucleotide Sequencing / methods*
  • High-Throughput Screening Assays
  • Humans
  • Pharmacogenetics / methods*
  • Phenotype
  • Sequence Analysis, DNA / methods