Theoretical basis for the identification of allelic variants that encode drug efficacy and toxicity

Min Lin, Rongling Wu

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Almost all drugs that produce a favorable response (efficacy) may also produce adverse effects (toxicity). The relative strengths of drug efficacy and toxicity that vary in human populations are controlled by the combined influences of multiple genes and emironmental influences. Genetic mapping has proven to be a powerful tool for detecting and identifying specific DNA sequence variants on the basis of the haplotype map (HapMap) constructed from single-nucleotide polymorphisms (SNPs). In this article, we present a novel statistical model for sequence mapping of two different but related drug responses. This model is incorporated by mathematical functions of drug response to varying doses or concentrations and the statistical device used to model the correlated structure of the residual (co)variance matrix. We implement a closed-form solution for the EM algorithm to estimate the population genetic parameters of SNPs and the simplex algorithm to estimate the curve parameters describing the pharmacodynamic changes of different genetic variants and matrix-structuring parameters. Extensive simulations are performed to investigate the statistical properties of our model. The implications of our model in pharmacogenetic and pharmacogenomic research are discussed.

Original languageEnglish (US)
Pages (from-to)919-928
Number of pages10
JournalGenetics
Volume170
Issue number2
DOIs
StatePublished - Jun 1 2005

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Drug-Related Side Effects and Adverse Reactions
Pharmacogenetics
Single Nucleotide Polymorphism
Pharmaceutical Preparations
Population Genetics
Statistical Models
Haplotypes
Equipment and Supplies
Research
Population
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

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Theoretical basis for the identification of allelic variants that encode drug efficacy and toxicity. / Lin, Min; Wu, Rongling.

In: Genetics, Vol. 170, No. 2, 01.06.2005, p. 919-928.

Research output: Contribution to journalArticle

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AU - Wu, Rongling

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