The human genome sequencing project provides the foundation for using individual genetics to optimize the selection and dosing of medications. The field of pharmacogenomics is still young, but has undergone a revolution in the last decade, as genomic technologies have uncovered associations between drug response phenotypes and genetic variations. The challenge now is to define the mechanisms underlying these associations, to advance our detailed understanding of the genetics of drug response. The PharmGKB (www.pharmgkb.org/) is devoted to collecting, encoding and disseminating knowledge about pharmacogenomics. PharmGKB is the pre-eminent resource for information about genes involved in the pharmacokinetics (PK) and pharmacodynamics of drug response, the pathways in which they act, and their important polymorphisms. PharmGKB staff curate this information, and have also helped lead successful international data sharing initiatives. In this proposal, we outline a plan to (1) curate information about genetic variations, pathways and networks relevant to drug response (2) create informatics tools for understanding the mechanism of drug response, (3) create and support new data sharing consortia, (4) engage in strategic collaborations to maximize PharmGKB's impact, and (5) disseminate the PharmGKB resources to the scientific community. We provide testimonials from users and letters of support from the research community to demonstrate our ongoing impact on the field.

Public Health Relevance

Pharmacogenomics is the study of how variations in human genes affect our response to drugs. It is the science behind personalized medicine-using individual genetics to increase the efficacy of drugs, and reduce their unwanted side effects. This proposal outlines a plan to extend the PharmGKB, a web-based resource that provides high-quality information and tools to researchers in pharmacogenomics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Resource-Related Research Projects (R24)
Project #
5R24GM061374-12
Application #
8100482
Study Section
Special Emphasis Panel (ZGM1-PPBC-5 (KB))
Program Officer
Long, Rochelle M
Project Start
2000-04-01
Project End
2015-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
12
Fiscal Year
2011
Total Cost
$3,000,025
Indirect Cost
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Bergmeijer, Thomas O; Reny, Jean-Luc; Pakyz, Ruth E et al. (2018) Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points-Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC). Am Heart J 198:152-159
Alvarellos, Maria; Guillemette, Chantal; Altman, Russ B et al. (2018) PharmGKB summary: atazanavir pathway, pharmacokinetics/pharmacodynamics. Pharmacogenet Genomics 28:127-137
Goetz, Matthew P; Sangkuhl, Katrin; Guchelaar, Henk-Jan et al. (2018) Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. Clin Pharmacol Ther 103:770-777
Li, Yong Fuga; Altman, Russ B (2018) Systematic target function annotation of human transcription factors. BMC Biol 16:4
Amstutz, Ursula; Henricks, Linda M; Offer, Steven M et al. (2018) Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103:210-216
Mallory, Emily K; Acharya, Ambika; Rensi, Stefano E et al. (2018) Chemical reaction vector embeddings: towards predicting drug metabolism in the human gut microbiome. Pac Symp Biocomput 23:56-67
Huddart, Rachel; Fohner, Alison E; Whirl-Carrillo, Michelle et al. (2018) Standardized biogeographic grouping system for annotating populations in pharmacogenetic research. Clin Pharmacol Ther :
Klein, Teri E; Ritchie, Marylyn D (2018) PharmCAT: A Pharmacogenomics Clinical Annotation Tool. Clin Pharmacol Ther 104:19-22

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