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A statistical model for functional mapping of quantitative trait loci regulating drug response

The Pharmacogenomics Journal volume 4, pages 315–321 (2004)Cite this article

ABSTRACT

Differential drug response, that is, pharmacodynamics, is most often likely to be a complex trait, controlled by the combined influences of multiple genes and environmental influences. Genetic mapping has proven to be a powerful tool for detecting and identifying specific genes affecting complex traits, that is, quantitative trait loci (QTL), based on polymorphic markers. In this article, we present a novel statistical model for genetic mapping of QTL governing pharmacodynamic processes. In principle, this model is a combination of functional mapping proposed to map function-valued traits and linkage disequilibrium mapping designed to provide high-resolution mapping of QTL by making use of recombination events created at a historic time. We implement a closed-form solution for the Expectation-Maximization algorithm to estimate the population genetic parameters of QTL and the simplex algorithm to estimate the curve parameters describing the pharmacodynamic changes of different QTL genotypes in response to drug dose or concentrations. Extensive simulations are performed to investigate the statistical properties of our model. The implications of our model in pharmacogenetic and pharmacogenomic research are discussed.

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Author notes

  1. Y Gong and Z Wang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Statistics, University of Florida, Gainesville, FL, USA

    Y Gong, Z Wang, T Liu, W Zhao, Y Zhu & R Wu

  2. Department of Pharmacy Practice, University of Florida, Gainesville, FL, USA

    J A Johnson

Authors
  1. Y Gong
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  2. Z Wang
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  3. T Liu
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  4. W Zhao
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  5. Y Zhu
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  6. J A Johnson
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  7. R Wu
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Corresponding author

Correspondence to R Wu.

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Gong, Y., Wang, Z., Liu, T. et al. A statistical model for functional mapping of quantitative trait loci regulating drug response. Pharmacogenomics J 4, 315–321 (2004). https://doi.org/10.1038/sj.tpj.6500262

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