Modeling sequence-sequence interactions for drug response.
BACKGROUND
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.


BACKGROUND
A computer program written in Matlab can be downloaded from the webpage of statistical genetics group at the University of Florida.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Lin
Min
M
Department of Statistics, University of Florida, Gainesville, FL 32611, USA.
Li
Hongying
H
Hou
Wei
W
Johnson
Julie A
JA
Wu
Rongling
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004280:Dobutamine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004843:Epistasis, Genetic; D005260:Female; D006239:Haplotypes; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D004280:Dobutamine