title: The global spectrum of protein-coding pharmacogenomic diversity.
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.
authors: 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.
authors: G E B
authors: GEB
authors: Wright
authors: 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.
authors: B
authors: B
authors: Carleton
authors: 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.
authors: M R
authors: MR
authors: Hayden
authors: BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.|Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors: C J D
authors: CJD
authors: Ross
mesh_terms: D000483:Alleles; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005828:Genetics, Population / Q000379:methods; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins