MOTIVATION: Genetic interactions or epistasis may play an important role in the genetic etiology of drug response. With the availability of large-scale, high-density single nucleotide polymorphism markers, a great challenge is how to associate haplotype structures and complex drug response through its underlying pharmacodynamic mechanisms. RESULTS: We have derived a general statistical model for detecting an interactive network of DNA sequence variants that encode pharmacodynamic processes based on the haplotype map constructed by single nucleotide polymorphisms. The model was validated by a pharmacogenetic study for two predominant beta-adrenergic receptor (betaAR) subtypes expressed in the heart, beta1AR and beta2AR. Haplotypes from these two receptors trigger significant interaction effects on the response of heart rate to different dose levels of dobutamine. This model will have implications for pharmacogenetic and pharmacogenomic research and drug discovery. AVAILABILITY: A computer program written in Matlab can be downloaded from the webpage of statistical genetics group at the University of Florida. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: Genetic interactions or epistasis may play an important role in the genetic etiology of drug response. With the availability of large-scale, high-density single nucleotide polymorphism markers, a great challenge is how to associate haplotype structures and complex drug response through its underlying pharmacodynamic mechanisms. RESULTS: We have derived a general statistical model for detecting an interactive network of DNA sequence variants that encode pharmacodynamic processes based on the haplotype map constructed by single nucleotide polymorphisms. The model was validated by a pharmacogenetic study for two predominant beta-adrenergic receptor (betaAR) subtypes expressed in the heart, beta1AR and beta2AR. Haplotypes from these two receptors trigger significant interaction effects on the response of heart rate to different dose levels of dobutamine. This model will have implications for pharmacogenetic and pharmacogenomic research and drug discovery. AVAILABILITY: A computer program written in Matlab can be downloaded from the webpage of statistical genetics group at the University of Florida. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Rongling Wu; Chunfa Tong; Zhong Wang; David Mauger; Kelan Tantisira; Stanley J Szefler; Vernon M Chinchilli; Elliot Israel Journal: Drug Discov Today Date: 2011-09-06 Impact factor: 7.851
Authors: Ming Li; Stephen W Erickson; Charlotte A Hobbs; Jingyun Li; Xinyu Tang; Todd G Nick; Stewart L Macleod; Mario A Cleves Journal: Genet Epidemiol Date: 2014-03-02 Impact factor: 2.135
Authors: Ming Li; Mario A Cleves; Himel Mallick; Stephen W Erickson; Xinyu Tang; Todd G Nick; Stewart L Macleod; Charlotte A Hobbs Journal: Hum Genet Date: 2014-06-04 Impact factor: 4.132