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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.

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


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.

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