Nature Genetics
37, 84 - 89 (2004)
Published online: 19 December 2004; | doi:10.1038/ng1488
A single-nucleotide polymorphism tagging set for human drug metabolism and transportKourosh R Ahmadi1, 5, Mike E Weale1, 5, Zhengyu Y Xue2, Nicole Soranzo1, David P Yarnall2, James D Briley2, Yuka Maruyama3, Mikiro Kobayashi3, Nicholas W Wood4, Nigel K Spurr2, Daniel K Burns2, Allen D Roses2, Ann M Saunders2
& David B Goldstein11
Department of Biology (Galton Lab), University College London, The Darwin Building, Gower Street, London WC1E 6BT, UK. 2
Genetics Research, GlaxoSmithKline, PO Box 13398, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA. 3
Genetics Research, Tsukuba Research Laboratories, GlaxoSmithKline, Wadai 43, Tsukuba, Ibaraki, 300-4247, Japan. 4
Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, WC1N 3BG, UK. 5
These authors contributed equally to this work.
Correspondence should be addressed to David B Goldstein d.goldstein@ucl.ac.ukInterindividual 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 drugs1. 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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