The global spectrum of protein-coding pharmacogenomic diversity

Pharmacogenomics J. 2018 Jan;18(1):187-195. doi: 10.1038/tpj.2016.77. Epub 2016 Oct 25.

Abstract

Differences in response to medications have a strong genetic component. By leveraging publically available data, the spectrum of such genomic variation can be investigated extensively. Pharmacogenomic variation was extracted from the 1000 Genomes Project Phase 3 data (2504 individuals, 26 global populations). A total of 12 084 genetic variants were found in 120 pharmacogenes, with the majority (90.0%) classified as rare variants (global minor allele frequency <0.5%), with 52.9% being singletons. Common variation clustered individuals into continental super-populations and 23 pharmacogenes contained highly differentiated variants (FST>0.5) for one or more super-population comparison. A median of three clinical variants (PharmGKB level 1A/B) was found per individual, and 55.4% of individuals carried loss-of-function variants, varying by super-population (East Asian 60.9%>African 60.1%>South Asian 60.3%>European 49.3%>Admixed 39.2%). Genome sequencing can therefore identify clinical pharmacogenomic variation, and future studies need to consider rare variation to understand the spectrum of genetic diversity contributing to drug response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Ethnicity / genetics
  • Gene Frequency / genetics
  • Genetic Variation / genetics*
  • Genetics, Population / methods
  • Humans
  • Pharmacogenetics / methods
  • Proteins / genetics*

Substances

  • Proteins