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Use of pairwise marker combination and recursive partitioning in a pharmacogenetic genome-wide scan

The Pharmacogenomics Journal volume 7, pages 180–189 (2007)Cite this article

Abstract

The objective of pharmacogenetic research is to identify a genetic marker, or a set of genetic markers, that can predict how a given person will respond to a given medicine. To search for such marker combinations that are predictive of adverse drug events, we have developed and applied two complementary methods to a pharmacogenetic study of the hypersensitivity reaction (HSR) associated with treatment with abacavir, a medicine that is used to treat HIV-infected patients. Our results show that both of these methods can be used to uncover potentially useful predictive marker combinations. The pairwise marker combination method yielded a collection of marker pairs that featured a spectrum of sensitivities and specificities. Recursive partitioning results led to the genetic delineation of multiple risk categories, including those with extremely high and extremely low risk of HSR. These methods can be readily applied in pharmacogenetic candidate gene studies as well as in genome-wide scans.

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Acknowledgements

This research would not have been possible without the participation of literally thousands of individuals. We thank the patients and the healthcare providers who generously contributed to these studies as well as the dedicated GSK staff who facilitated the conduct of these studies and provided critical laboratory and bioinformatic support. For a list of all the participating investigators, refer to the supplementary information. This work was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

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Authors and Affiliations

  1. GlaxoSmithKline, RTP, NC, USA

    L L Warren, A R Hughes, E H Lai, S A Haneline, A W Wooster, W R Spreen, J E Hernandez, T R Scott, A D Roses & M Mosteller

  2. National Institute of Environmental Health Sciences, RTP, NC, USA

    D V Zaykin

  3. GlaxoSmithKline, Harlow, Essex, UK

    A T Bansal

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  1. L L Warren
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  2. A R Hughes
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  3. E H Lai
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  4. D V Zaykin
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  6. A T Bansal
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  7. A W Wooster
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  8. W R Spreen
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  9. J E Hernandez
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  10. T R Scott
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  11. A D Roses
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  12. M Mosteller
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on behalf of the CNA30027 and CNA30032 study teams

Corresponding author

Correspondence to M Mosteller.

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None declared.

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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Warren, L., Hughes, A., Lai, E. et al. Use of pairwise marker combination and recursive partitioning in a pharmacogenetic genome-wide scan. Pharmacogenomics J 7, 180–189 (2007). https://doi.org/10.1038/sj.tpj.6500414

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