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

The global spectrum of protein-coding pharmacogenomic diversity.

Author information

1
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
2
BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
3
Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
4
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.

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‚ÄČ084 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.

PMID:
27779249
PMCID:
PMC5817389
DOI:
10.1038/tpj.2016.77
[Indexed for MEDLINE]
Free PMC Article

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