| Modeling the genetic etiology of pharmacokinetic-pharmacodynamic links with the ARMA process. | |
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MedLine Citation:
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PMID: 20309763 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Substantial variability exists among different patients in response to drugs. The identification of genetic factors that contribute to the interpersonal differentiation has been an important task for pharmacogenetic research and drug discovery. In this article, we have derived a high-dimensional statistical model for unveiling the genetic machinery for drug response by integrating two different but biologically related processes--pharmacokinetics (PK) and pharmacodynamics (PD)--into a genetic mapping framework. Using an integrated model of PK and PD, we can identify specific DNA sequence variants and test how they relate to the differential effect of the body to the drug (PK) and the effect of the drug on the body (PD). To effectively model a two-stage hierarchic structure of the covariance matrix at the PD and PK level, we have for the first time introduced an autoregressive moving-average (ARMA) process to the mixture-based likelihood function for sequence mapping. Closed-form estimates of the determinant and inverse of the ARMA-based covariance matrix are incorporated into the estimation step, which significantly increases the computational efficiency. Simulation studies have been performed to test the statistical behavior of our model. Potential applications of this model to pharmacogenetic research are discussed. |
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Authors:
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Min Lin; Arthur Berg; Rongling Wu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of biopharmaceutical statistics Volume: 20 ISSN: 1520-5711 ISO Abbreviation: J Biopharm Stat Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-23 Completed Date: 2010-06-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9200436 Medline TA: J Biopharm Stat Country: England |
Other Details:
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Languages: eng Pagination: 351-72 Citation Subset: IM |
Affiliation:
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Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA. annie.lin@duke.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Computer Simulation Data Interpretation, Statistical Dose-Response Relationship, Drug Haplotypes Humans Likelihood Functions Models, Statistical* Pharmacogenetics / statistics & numerical data* Pharmacokinetics* Polymorphism, Single Nucleotide Reproducibility of Results Risk Assessment Risk Factors Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
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0540745//PHS HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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