Thursday, May 19, 2016

Pharmacogenetics in Scientific American

Dina Fine Maron discusses pharmacogenetics and pharmacogenomics (PGx) in a new video and article titled “A Very Personal Problem” in this week’s issue of Scientific American. In that article, Fine Maron describes the science of PGx and tells the personal stories of two pediatric patients who received care at St. Jude’s. She also includes discussions with Dr. Mary Relling, co-principal investigator of the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dr. Dan Roden, CPIC steering committee member. CPIC is a shared project with PharmGKB and the Pharmacogenetics Research Network (PGRN). In the article, Dr. Relling and Dr. Roden discuss the utility of and impediments to pre-emptive PGx testing and how their respective institutions have successfully implemented pre-emptive PGx testing as a routine part of care. The CPIC dosing guidelines for all gene-drug pair interactions that were discussed in the article (CYP2D6 and codeine, CYP2C19 and clopidogrel, SLCO1B1 and simvastatin and G6PD and rasburicase) and a list of institutions that are currently implementing PGx testing can be found on the CPIC and PharmGKB websites. 

Wednesday, May 11, 2016

European Union awards €15 million to U-PGx consortium

The European Union H2020 programme has awarded a €15 million grant to the Ubiquitous Pharmacogenomics (U-PGx) consortium for an international pharmacogenomics research and implementation project.

The aim of the U-PGx consortium is to make actionable pharmacogenomic data and effective treatment optimization accessible to every European citizen. The objective of the research and implementation project is to map genetic profiles of 8,000 patients, and then implement stratified prescribing of drugs in these patients based on the Dutch Pharmacogenetics Working Group guidelines. The cost-effectiveness and clinical-effectiveness of this approach will then be evaluated. Educational activities are also planned to assist in the training and education of health care professionals and patients regarding pharmacogenomics.

U-PGx will host its 1st annual consortium meeting in Athens, Greece in September 2016; Teri Klein, co-principal investigator of PharmGKB and the Clinical Pharmacogenetics Implementation Consortium (CPIC), will be in attendance. Dr. Russ Altman, co-principal investigator of PharmGKB, is on the advisory board for U-PGx.

Visit the U-PGx website

Tuesday, May 10, 2016

Evidence of pharmacogenetics in aiding polypharmacy outcomes

Many drugs interact with the same enzymes and transporters. As a result, variation in the genes encoding these proteins can affect risks of side effects and likelihood of treatment success for patients taking many medications. These interactions may be different and not necessarily predicted from trials of single drugs. Knowing a patient’s genotypes for pharmacogenes can help optimize these treatment regimes. PharmGKB provides resources for exploring these relationships between genetic variation and drug response.

The recent article, “Potential utility of precision medicine for older adults with polypharmacy: a case series study” illustrates increased risk of hospitalization in patients taking multiple medications who also have variants in cytochrome P450 genes. Finkelstein, et al. present the cases of 3 older adults with chronic heart and lung disease, who were taking between 17 and 26 medications each. One of these patients had genotypes predicting normal metabolizer status for CYP2C19, CYP2C9, CYP2D6, and CYP3A4/5. This patient had no hospitalizations in the previous 5 years. The other two patients, one who was a CYP2D6 rapid metabolizer and the other who was a CYP3A4/5 poor metabolizer, had 6 and 23 hospitalizations related to adverse cardiovascular events. While this is a small number of cases, it illustrates the power of pharmacogenomics in optimizing medication regimes in cases of polypharmacy.

Wednesday, April 20, 2016

Introducing the new PharmGKB Cancer PGx Portal

PharmGKB has collected a number of resources for Cancer PGx into one easy location. There are tables with direct links to genes important for cancer drug response both for PD and PK, to cancer drug pathways, particular cancers that have PGx data, types of toxicities common to cancer drugs, and external resources.

Eight new VIP gene pages give a short text based summary of important genes for cancer drug response. These are for the genes ALK, ABL1, BCR, BRAF, ERBB2 (HER2), KIT, KRAS and NRAS. Anyone with expertise in the genes who wishes to develop these with us for publication in PG&G, please contact feedback.

There is a shortlist of drug labels for cancer drugs with biomarker PGx.

We currently have 34 anti-cancer agent drug pathways with 8 new pathways in development. The portal gives shortcuts to a selection.

PharmGKB currently uses a flat ontology for diseases, which means that the Neoplasms disease page does not link to the many different cancers we have data for. The cancer portal has direct links to the cancers for which there is the most PGx information in the knowledgebase, such as pediatric ALL, CML, colorectal, breast, renal and non-small cell lung cancers. The portal also has links to the common types of toxicities with PGx data.

Finally there is a collection of external links that are useful for Cancer PGx.

Tuesday, April 19, 2016

Top 100 Prescribed Drugs with CPIC Guidelines

Pharmacogenetics has important consequences for some of the most commonly prescribed medications. Depending on the source and structure of the list, the 100 most commonly prescribed drugs include between 3 (RxList from the Medscape report of August 2014 ) and 16 (Pharmacy student study guide drugs with CPIC recommendations.  CPIC guidelines offer recommendations for changes to drug choice or drug dose based on patient genotype, with important implications for efficacy and toxicity, and can be found at  In the RxList, the drugs with CPIC guidelines are rosuvastatin, simvastatin, and atorvastatin. In the pharmacy study list, the drugs with CPIC guidelines are citalopram, escitalopram, warfarin, clopidogrel, amitriptyline, paroxetine, sertraline, oxycodon, codeine, allopurinol, and the 5 statins simvastatin, rosuvastatin, pravastatin, atorvastatin, and lovastatin. In addition, the illustrated pharmacokinetic and pharmacodynamics pathways developed and freely available on the PharmGKB website contain 37 of the drugs found on the pharmacy study list.

Friday, April 15, 2016

Pharmacogenomics Clinical Annotation Tool (PharmCAT)

An active area of genomic medicine implementation at many health care organizations and academic medical centers includes development of decision support and return of results around pharmacogenomics.  The Clinical Pharmacogenetics Implementation Consortium (CPIC) has established guidelines surrounding gene-drug pairs that can and should lead to treatment modifications based on genetic variants.  One of the challenges in implementing pharmacogenomics is the representation of the information in the CPIC guidelines (including star-alleles) and extracting these variants and haplotypes from genetic datasets.  In a collaboration between the PGRN Statistical Analysis Resource (P-STAR), the Pharmacogenomics Knowledgebase (PharmGKB), the Clinical Genome Resource (ClinGen), and CPIC, we are developing a software tool to extract all CPIC level-A variants from a genetic dataset (represented as a vcf), interpret the variant alleles, and generate a report.  The CPIC pipeline report can then be used to make future treatment decisions. 

We assembled a focus group of thought leaders in pharmacogenomics to brainstorm and design the software pipeline.  We hosted a one-week Hackathon at the PharmGKB at Stanford University to bring together computer programmers with scientific curators to implement version one of this tool.  We will host a meeting to summarize and evaluate next steps in mid-May including the development of a manuscript and dissemination plan for the tool.  This software pipeline will be made available in a Creative Commons license and disseminated in GitHub later this spring for all in the scientific community to test, explore, improve and to give us feedback.  Be a part of this project!  As many of our institutions are building implementation workflows for pharmacogenomics, our ability to automate some of the extraction of genes/variants of interest would be enormously helpful.

We welcome scientific input from our colleagues.  If you would like to become involved in this effort, we ask that you contact  Thank you!

Thursday, March 31, 2016

CPIC Informatics Working Group publishes article in JAMIA

An article from the Clinical Pharmacogenetics Implementation Consortium (CPIC) Informatics Working Group has now been published ahead-of-print on the Journal of the American Medical Informatics Association (JAMIA) website. Within the paper, the authors discuss principles that will support the implementation of precision medicine, particularly pharmacogenomics, into routine clinical care.                                                                                

Hoffman et al. write that successful adoption of pharmacogenomics in the clinic requires a database of knowledge that can be used in an electronic health record (EHR) with Clinical Decision Support (CDS). To this end, the CPIC Informatics Working group has been developing and incorporating EHR vendor-agnostic resources into CPIC guidelines. Based on this experience, the working group outlines five principles that can apply to future knowledge resources that implement precision medicine. Though the principles are mainly in reference to pharmacogenomics, they are applicable any type of precision medicine initiative. The five principles cover the limitations of current genetic testing methods, the importance of levels of evidence, integration of different types of medical knowledge and handling of new knowledge, and the use of standardized terminology. By laying out these principles, the CPIC Informatics Working Group provides a reference for the design and implementation of future, national-level precision medicine resources.

CPIC is a shared project between PharmGKB and the Pharmacogenomics Research Network. Read more about CPIC and the Informatics Working Group at

Read the paper on JAMIA:

Developing knowledge resources to support precision medicine: principles from the Clinical Pharmacogenetics Implementation Consortium (CPIC). James M. Hoffman; Henry M Dunnenberger; J Kevin Hicks; Kelly E Caudle; Michelle Whirl Carrillo; Robert R Freimuth; Marc S Williams; Teri E Klein; Josh F Peterson. Journal of the American Medical Informatics Association 2016; doi: 10.1093/jamia/ocw027.