{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T20:50:55Z","timestamp":1770843055115,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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.<\/jats:p><jats:p>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 (\u03b2AR) subtypes expressed in the heart, \u03b21AR and \u03b22AR. 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.<\/jats:p><jats:p>Availability: A computer program written in Matlab can be downloaded from the webpage of statistical genetics group at the University of Florida.<\/jats:p><jats:p>Contact: \u00a0rwu@mail.ifas.ufl.edu<\/jats:p><jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm110","type":"journal-article","created":{"date-parts":[[2007,3,29]],"date-time":"2007-03-29T00:32:41Z","timestamp":1175128361000},"page":"1251-1257","source":"Crossref","is-referenced-by-count":23,"title":["Modeling sequence\u2013sequence interactions for drug response"],"prefix":"10.1093","volume":"23","author":[{"given":"Min","family":"Lin","sequence":"first","affiliation":[{"name":"1 Department of Statistics, 2Department of Epidemiology and Health Policy Research, 3Department of Pharmacy Practice, University of Florida, Gainesville, FL 32611 and 4Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27715, USA"},{"name":"1 Department of Statistics, 2Department of Epidemiology and Health Policy Research, 3Department of Pharmacy Practice, University of Florida, Gainesville, FL 32611 and 4Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27715, USA"}]},{"given":"Hongying","family":"Li","sequence":"additional","affiliation":[{"name":"1 Department of Statistics, 2Department of Epidemiology and Health Policy Research, 3Department of Pharmacy Practice, University of Florida, Gainesville, FL 32611 and 4Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27715, USA"}]},{"given":"Wei","family":"Hou","sequence":"additional","affiliation":[{"name":"1 Department of Statistics, 2Department of Epidemiology and Health Policy Research, 3Department of Pharmacy Practice, University of Florida, Gainesville, FL 32611 and 4Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27715, USA"}]},{"given":"Julie A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"1 Department of Statistics, 2Department of Epidemiology and Health Policy Research, 3Department of Pharmacy Practice, University of Florida, Gainesville, FL 32611 and 4Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27715, USA"}]},{"given":"Rongling","family":"Wu","sequence":"additional","affiliation":[{"name":"1 Department of Statistics, 2Department of Epidemiology and Health Policy Research, 3Department of Pharmacy Practice, University of Florida, Gainesville, FL 32611 and 4Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27715, USA"}]}],"member":"286","published-online":{"date-parts":[[2007,3,28]]},"reference":[{"key":"2023041104483897700_","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2174\/1570160033476287","article-title":"Pharmacogenetic and pharmacogenomic research in psychiatry: current advances and clinical applications","volume":"1","author":"Arranz","year":"2003","journal-title":"Curr. 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