Exome-Wide Analysis of the DiscovEHR Cohort Reveals Novel Candidate Pharmacogenomic Variants for Clinical Pharmacogenomics

Genes (Basel). 2020 May 18;11(5):561. doi: 10.3390/genes11050561.

Abstract

Recent advances in next-generation sequencing technology have led to the production of an unprecedented volume of genomic data, thus further advancing our understanding of the role of genetic variation in clinical pharmacogenomics. In the present study, we used whole exome sequencing data from 50,726 participants, as derived from the DiscovEHR cohort, to identify pharmacogenomic variants of potential clinical relevance, according to their occurrence within the PharmGKB database. We further assessed the distribution of the identified rare and common pharmacogenomics variants amongst different GnomAD subpopulations. Overall, our findings show that the use of publicly available sequence data, such as the DiscovEHR dataset and GnomAD, provides an opportunity for a deeper understanding of genetic variation in pharmacogenes with direct implications in clinical pharmacogenomics.

Keywords: PGx variants; PharmGKB; Pharmacogenomics; allele distribution; gnomAD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Data Management
  • Databases, Genetic
  • Exome / genetics
  • Exome Sequencing / methods
  • Female
  • Genomics*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • Metabolic Detoxication, Phase I / genetics
  • Metabolic Detoxication, Phase II / genetics
  • Pharmacogenetics*
  • Pharmacogenomic Variants / genetics*
  • Polymorphism, Single Nucleotide / genetics