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

Warren LL, Hughes AR, Lai EH, Zaykin DV, Haneline SA, Bansal AT, Wooster AW, Spreen WR, Hernandez JE, Scott TR, Roses AD, Mosteller M,

GlaxoSmithKline, RTP, NC 27709, USA.

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.

Published 23 May 2007 in Pharmacogenomics J, 7(3): 180-9.
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