Abstract
Pharmacogenomically relevant markers of drug response and adverse drug reactions are known to vary in frequency across populations. We examined minor allele frequencies (MAFs), genetic diversity (FST) and population structure of 1156 genetic variants (including 42 clinically actionable variants) in 212 genes involved in drug absorption, distribution, metabolism and excretion (ADME) in 19 populations (n=1478). There was wide population differentiation in these ADME variants, reflected in the range of mean MAF (ΔMAF) and FST. The largest mean ΔMAF was observed in African ancestry populations (0.10) and the smallest mean ΔMAF in East Asian ancestry populations (0.04). MAFs ranged widely, for example, from 0.93 for single-nucleotide polymorphism (SNP) rs9923231, which influences warfarin dosing to 0.01 for SNP rs3918290 associated with capecitabine metabolism. ADME genetic variants show marked variation between and within continental groupings of populations. Enlarging the scope of pharmacogenomics research to include multiple global populations can improve the evidence base for clinical translation to benefit all peoples.
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Acknowledgements
The informatics expertise of Kevin Long, University of North Carolina, Chapel Hill is greatly appreciated. The study was supported by National Institutes of Health grants S06GM008016-320107 to CNR and S06GM008016-380111 to AA. HUFS participants were enrolled at the Howard University General Clinical Research Center, which is supported by grant 2M01RR010284 from the former National Center for Research Resources, National Institutes of Health. This research was supported in part by the Intramural Research Program of the Center for Research on Genomics and Global Health. The Center for Research on Genomics and Global Health is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology and the Office of the Director at the National Institutes of Health (Z01HG200362).
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Ramos, E., Doumatey, A., Elkahloun, A. et al. Pharmacogenomics, ancestry and clinical decision making for global populations. Pharmacogenomics J 14, 217–222 (2014). https://doi.org/10.1038/tpj.2013.24
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DOI: https://doi.org/10.1038/tpj.2013.24
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