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The use of single-nucleotide polymorphism maps in pharmacogenomics

Nature Biotechnology volume 18, pages 505–508 (2000)Cite this article

Abstract

Single-nucleotide polymorphisms (SNPs), common variations among the DNA of individuals, are being uncovered and assembled into large SNP databases that promise to enable the dissection of the genetic basis of disease and drug response (i.e., pharmacogenomics). Although great strides have been made in understanding the diversity of the human genome, such as the frequency, distribution, and type of genetic variation that exists, the feasibility of applying this information to uncover useful pharmacogenomic markers is uncertain. The health care industry is clamoring for access to SNP databases for use in research in the hope of revolutionizing the drug development process. As the reality of using SNPs to uncover drug response markers is rarely addressed, this review discusses practical issues, such as patient sample size, SNP density and genome coverage, and data interpretation, that will be important for determining the applicability of pharmacogenomic information to medical practice.

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Figure 1: Graph demonstrating the effect of varying linkage disequilibrium (D′) on relative risk using data from scenario 3 in Table 1.
Figure 2: Sample sizes required for detecting the association outlined in scenario 6 from Table 1, using an LD mapping approach with varying numbers of SNP markers and varying degrees of LD.

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Acknowledgements

We wish to especially thank Joanne Meyer and Steve Lewitzky for critical review of the manuscript and comments.

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Authors and Affiliations

  1. Millennium Predictive Medicine, Inc., MA 02139, Cambridge

    Jeanette J. McCarthy

  2. Solvias AG, Basel, Switzerland

    Rolf Hilfiker

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Correspondence to Jeanette J. McCarthy.

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McCarthy, J., Hilfiker, R. The use of single-nucleotide polymorphism maps in pharmacogenomics. Nat Biotechnol 18, 505–508 (2000). https://doi.org/10.1038/75360

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