A single-nucleotide polymorphism tagging set for human drug metabolism and transport |
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Authors: | Ahmadi Kourosh R Weale Mike E Xue Zhengyu Y Soranzo Nicole Yarnall David P Briley James D Maruyama Yuka Kobayashi Mikiro Wood Nicholas W Spurr Nigel K Burns Daniel K Roses Allen D Saunders Ann M Goldstein David B |
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Institution: | Department of Biology (Galton Lab), University College London, The Darwin Building, Gower Street, London WC1E 6BT, UK. |
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Abstract: | Interindividual variability in drug response, ranging from no therapeutic benefit to life-threatening adverse reactions, is influenced by variation in genes that control the absorption, distribution, metabolism and excretion of drugs. We genotyped 904 single-nucleotide polymorphisms (SNPs) from 55 such genes in two population samples (European and Japanese) and identified a set of tagging SNPs that represents the common variation in these genes, both known and unknown. Extensive empirical evaluations, including a direct assessment of association with candidate functional SNPs in a new, larger population sample, validated the performance of these tagging SNPs and confirmed their utility for linkage-disequilibrium mapping in pharmacogenetics. The analyses also suggest that rare variation is not amenable to tagging strategies. |
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