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Chapter 7: Pharmacogenomics
- Konrad J. Karczewski,
- Roxana Daneshjou,
- Russ B. Altman mail
- There is great variation in drug-response phenotypes, and a “one size fits all” paradigm for drug delivery is flawed. Pharmacogenomics is the study of how human genetic information impacts drug response, and it aims to improve efficacy and reduced side effects. In this article, we provide an overview of pharmacogenetics, including pharmacokinetics (PK), pharmacodynamics (PD), gene and pathway interactions, and off-target effects. We describe methods for discovering genetic factors in drug response, including genome-wide association studies (GWAS), expression analysis, and other methods such as chemoinformatics and natural language processing (NLP). We cover the practical applications of pharmacogenomics both in the pharmaceutical industry and in a clinical setting. In drug discovery, pharmacogenomics can be used to aid lead identification, anticipate adverse events, and assist in drug repurposing efforts. Moreover, pharmacogenomic discoveries show promise as important elements of physician decision support. Finally, we consider the ethical, regulatory, and reimbursement challenges that remain for the clinical implementation of pharmacogenomics.
Citation: Karczewski KJ, Daneshjou R, Altman RB (2012) Chapter 7: Pharmacogenomics. PLoS Comput Biol 8(12): e1002817. doi:10.1371/journal.pcbi.1002817
Editors: Fran Lewitter ( Whitehead Institute, United States of America ), and Maricel Kann (University of Maryland, Baltimore County, United States of America)
Published: December 27, 2012
Copyright: © 2012 Karczewski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: KJK is supported by NIH/NLM National Library of Medicine training grant “Graduate Training in Biomedical Informatics” T15-LM007033 and the NSF Graduate Research Fellowship Program. RD is supported by Stanford Medical Scholars. RBA is supported by PharmGKB GM61374. The funders had no role in the preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: russ.altman@stanford.edu
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