Sunday, December 20, 2015

ACMG Issues a Revised Position Statement Regarding DTC Genetic Testing

The American College of Medical Genetics (ACMG) recently revised its position statement regarding direct-to-consumer (DTC) genetic testing. Briefly, the ACMG recommends that:

  • Knowledgeable professionals order the genetic test, which should be undertaken by a Clinical Laboratory Improvement Amendments (CLIA) accredited laboratory.
  • Board certified genetics experts, such as clinical geneticists, or genetic counselors should be available to assist with test interpretation
  • DTC genetic tests should incorporate family history and patient-specific information into result reports, which should be presented in a manner that is comprehensible by the consumer.
  • Consumers should be informed of the possibility of incidental findings and of the implications of these incidental findings for relatives.
  • The scientific evidence underlying the validity and utility of a genetic test should be explicitly stated. 
  • Consumers should be made aware of where test results will be stored, as well as the identities of the parties that will have access to the test results. 

Read the revised ACMG position statement.

Thursday, December 17, 2015

DIGITizE Suggests Implementing 2 CPIC Guidelines in CDS

The DIGITizE Action Collaborative has suggested that Clinical Decision Support (CDS) be implemented based on CPIC's TPMT/azathioprine and HLA-B/abacavir guidelines.  DIGITizE (Displaying and Integrating Genetic Information Through the EHR) is a collaborative group of the Institute of Medicine consisting of key stakeholders interested in integrating genomic information into electronic health records (EHR).  As part of their efforts to create support for a few very specific use cases, they have chosen to focus on the impact of (1) HLA-B*57:01 on abacavir hypersensitivity and (2) TPMT alleles on azathioprine dosing, consistent with the CPIC guidelines.  They recommend having patient genotypes in the EHR before prescribing these medications.

CPIC guidelines can be found on PharmGKB for TPMT/azathioprine and HLA-B/abacavir.

Friday, December 11, 2015

Combining large PGx datasets from cancer cell lines

Testing cancer cell lines in vitro for drug sensitivity is a cornerstone of preclinical drug development. Large publically available datasets can be found at The Genomics of Drug Sensitivity in Cancer Project (GDSE) and The Cancer Cell Line Encyclopedia (CCLE).

Studies attempting to combine large public datasets and analyzing for correlation questioned the reliability of the data due to limited concordance, reported in [PMID: 24284626], discussed in [PMID:24284624] and a confirmation study here.

A new report in Nature describes different methods to analyze the data from CCLE and GDSE and concludes that “data from either study yields similar predictors of drug response” [PMID:26570998].

These papers demonstrate the continuing difficulty trying to compare across large datasets. Such problems include comparing different experimental protocols and measurements for drug sensitivity across studies, trouble matching the drug and cell line names to ensure like comparison, discordance in the genotyping data, and drugs that had few examples of cell lines that were drug sensitive.  As always, attention to detail in the documentation and description of the experiments can help mitigate some of these difficulties. While development of standard testing protocols and data curation and reporting frameworks may lead to better validation of drug response predictors going forward there will always be the need for methods to filter the noise that is inevitable in large datasets.

Wednesday, December 9, 2015

ASHP Foundation Recognizes Clinical Implementation of PGx

The University of Illinois (UI) Personalized Medicine Program led by Dr. Edith Nutescu, is one of three finalists for the 2015 Award for Excellence in Medication-Use Safety, which is given by the American Society of Health-Systems Pharmacists (ASHP) Foundation. The program at the UI Hospital and Health Sciences System has genotyped over 1,500 patients to help guide warfarin and clopidogrel dosing. According to Dr. Nutescu, the program has led to significant decreases in hospital readmission rates due to drug-related adverse events, while simultaneously saving UI health an estimated $600,000 annually. 

Read the UIC press release: 

The Clinical Pharmacogenetics Implementation Consortium (CPIC) dosing guidelines are available for warfarin and clopidogrel

Interactive pharmacokinetic (PK) and pharmacodynamic (PD) pathway summaries for warfarin (PD and PK) and clopidogrel (PK and PD ) are also available on PharmGKB.

CPIC Upcoming Meetings - Save the Date!

The Clinical Pharmacogenetics Implementation Consortium is holding a meeting for members in 2016 and an open meeting in 2017.

CPIC Luncheon Meeting (open to CPIC members)
Thursday March 10th, 2016 Noon-1:30 PM
Hilton Bayfront Hotel, San Diego, CA
Email: to attend

CPIC Meeting (a specialty meeting of the PGRN)
Wednesday March 15th, 2017
Marriott Wardman Park Hotel,  Washington DC
Further details pending

Monday, December 7, 2015

Framework Published to Guide Development of PGx Public Policy, Applied in Canada

The paper, “The 3-I framework: a framework for developing public policies regarding pharmacogenomics (PGx) testing in Canada” was published last week in NRC Research Press. It presents a political science framework of considering ideas, interests, and institutions to identify challenges and needs for PGx implementation. The analysis is presented as a tool to guide policy development, with the goal of increasing PGx usage in clinical care. The article gives a review of the status of PGx policy and needs in Canada now, and compares it to key policies in other countries. These policies include the Genetic Information Nondiscrimination Act in the US and the contracts to prevent the disclosure of direct-to-consumer testing results to insurers in the UK.  We present this article as an example of conversations and tools around PGx policy development, and of how different countries are approaching the increasing usage of PGx in clinical care. If you are interested in learning more about implementation guidelines in the US, see the Clinical Pharmacogenetics Implementation Consortium (CPIC) at

Thursday, November 26, 2015

R.I.P. David Flockhart

It is with sadness that we let the PGx community know of the passing of our colleague and friend David Flockhart. May he be in a more peaceful place.

Saturday, November 21, 2015

Article on PGx by Dean Julie A. Johnson in The Conversation

Dean Julie A. Johnson, Dean of the College of Pharmacy, Distinguished Professor of Pharmacy and Medicine, and Director of the University of Florida Health Personalized Medicine Program at University of Florida published an article in The Conversation on November 20th, 2015 providing an overview of pharmacogenetics. Within the article, Dean Johnson explains the meaning of pharmacogenetics, and then provides two clinically relevant examples of pharmacogenetic associations.

The first example involving treatment of childhood leukemia is the TPMT gene and a class of chemotherapy drugs known as thiopurines. Dean Johnson notes that individuals whose TPMT enzyme does not work properly are given one-tenth the normal dosage of thiopurines, as recommended in guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC). These patients carry two copies of a non-functional TPMT allele, such as *2 or *3A, and are at a 100% risk of developing life-threatening myelosuppression if they receive a normal dose of thiopurines. CPIC also recommends thrice weekly as opposed to daily dosing of thiopurines for these patients, and recommends a dose reduction of 30-50% in individuals who carry one non-functional TPMT allele.

The second example is focused on the CYP2C19 gene and clopidogrel therapy. The CYP2C19 enzyme is the major enzyme responsible for the biotransformation of clopidogrel into its active metabolite. Approximately 25-30% of individuals have a CYP2C19 enzyme with reduced function due to the presence of CYP2C19 alleles such as *2 or *3. These individuals cannot fully convert clopidgrel to its active form, resulting in reduced efficacy of the drug. Dean Johnson cites the CPIC recommendations for clopidogrel, which suggest using an alternative drug in patients who carry CYP2C19 reduced function alleles. She also notes that a study undertaken at the University of Florida showed that when these types of patients were given an alternative drug, they had significantly fewer heart attacks and strokes, and were less likely to die as compared to patients who continued taking clopidogrel.

PharmGKB worked in partnership with the University of Florida Health Personalized Medicine Program on the implementation of pharmacogenetics in medicine, specifically on the creation of a customized genotyping panel for use within their personalized medicine program.

Read the article:

The Conversation - How your genes influence what medicines are right for you

The CPIC guidelines for thiopurine and clopidogrel therapy are available online at PharmGKB


Read the CPIC guidelines for thiopurine dosing and clopidogrel therapy:

Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Klein TE; Clinical Pharmacogenetics Implementation Consortium. Clin Pharmacol Ther. 2011 Dec;90(6):894. PMID: 21270794

Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-219 (CYP2C19) genotype and clopidogrel therapy. Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot JS, Johnson JA, Roden DM, Klein TE, Shuldiner AR; Clinical Pharmacogenetics Implementation Consortium. Clin Pharmacol Ther. 2011 Aug;90(2):328-32. PMID: 21716271

Friday, November 13, 2015

Associate Director of PharmGKB Discussing Database Curation and Genetic Test Interpretation at FDA Workshop

The adoption of next generation sequencing (NGS) in research and clinical practice has led to a rapidly expanding catalog of novel and rare genetic variants. However, the lack of robust statistical evidence to link novel and rare variants to specific phenotypes makes variant interpretation difficult. This is critically important as manufacturers of in vitro diagnostic tests (IVD) must provide evidence that a test supports its claimed intended use to the Food and Drug Administration (FDA).

With the goal to adopt an adaptive regulatory approach to NGS tests the FDA is holding a Public Workshop today, November 13, to discuss the role of public genetic databases in establishing the clinical relevance of rare and novel variants. Michelle Whirl-Carrillo, Associate Director of PharmGKB, is on Panel 2 to discuss database curation and clinical interpretation of genetic test results at 11:00 am EST. 

For more information, including an agenda and a link to a webcast of the workshop, click on the link below:

Thursday, November 5, 2015

Concordance of Drug Labels and Clinical Annotations

Some drug labels have been identified by the FDA as containing pharmacogenetic biomarker information, but occasionally these variants are not listed in the Clinical Annotations on PharmGKB. The Clinical Annotations are based on literature available in peer reviewed journals and focus on germline variants. As a result, there are a few reasons why variants identified in drug labels may not be found in PharmGKB Clinical Annotations.

  1. Data used to create the drug labels are not publicly available. Research conducted by pharmaceutical companies, such as trials done for drug approval, may be proprietary information and/or not be published, but are used by the FDA. Only published literature is curated in PharmGKB.  

  1. FDA labels may be based on drug classes but Clinical Annotations are drug specific. For example, the label of Protriptyline contains information about CYP2D6 but it is unknown whether proprietary information or drug class generalizations were used for this associations. Protriptyline is a tricyclic antidepressant. While no literature is available in a PubMed search for pharmacogenetics of protriptyline itself, the protriptyline drug label has a precaution for all tricyclic antidepressants, warning that poor metabolizers via CYP2D6 have higher plasma concentrations of tricyclic antidepressants generally.

  1. Data are based on studies that do not identify specific variants or that are done on functional protein assays. Clinical Annotations are written about specific SNPs or haplotypes, not for genes or pathways generally. For example, Tetrabenazine is used to treat hyperkinetic movement disorder, such as in Huntington’s Disease, and CYP2D6 testing is required by the FDA. The study describing altered metabolism of tetrabenazine based on CYP2D6 metabolizer status (Mehanna, 2013) classifies CYP2D6 metabolizer status by phenotypes but does not include any specific genotyping information. As a result, there are no variants to annotate in the case of tetrabenazine, though altered CYP2D6 activity has been associated with tetrabenazine response. Another example is valproic acid, which is contraindicated in patients with Urea Cycle Disorders (UCD). Therefore, genetic variation in any of the genes involved in the urea cycle is actionable, but not specifically annotatable.

  1. Relevant variation is in tumor cells and not germline. Cancer drugs that target tumors may be active or inactive based on mutations in the tumor cells. These drugs include afatinib, which is used to treat non-small cell lung cancer with EGFR mutations. Because these mutations occur in the tumor cells and are not part of the germline DNA, they are not covered extensively in PharmGKB, though we are working on ways to expand coverage.

  1. PharmGKB does not have the resources to cover all the articles of PubMed, and some annotations may not be curated yet. For routine curation, we focus on journals with a high volume of pharmacogenetics articles. Articles published in other journals may lag behind in curation. If you know articles that you think should be added to curation, please send them to

Monday, October 26, 2015

International Workgroup Recommendations for Pharmacogenetic Test Result Reporting

Lack of standardization in gene nomenclature systems and inconsistencies between laboratory reports of genetic test results have been identified as significant barriers to the implementation of (PGx) information in the clinic.  PharmGKB members Teri Klein, Katrin Sangkuhl, and Michelle Whirl-Carrillo were part of an international workgroup of pharmacogenomic (PGx) experts that was organized by the Centers for Disease Control and Prevention (CDC) to make recommendations for the description and reporting of variants in PGx relevant genes. The workgroup consensus recommendations include standardizing PGx gene nomenclature by utilizing widely accepted nomenclature systems (e.g. use of HGNC gene symbols, HGVS nomenclature), as well as standardizing clinical reporting of genetic test results and genetic test descriptions (e.g. listing the variants that were observed in the test, and a publicly available description of the test). These recommendations were recently published in Clinical Pharmacology and Therapeutics.

Read the recommendations below:

Wednesday, October 21, 2015

Pharmacogenomics in the clinic: Review article in this week's Nature

In the most recent edition of Nature, Dr. Mary Relling and Dr. William Evans provide a review of pharmacogenomic implementation in the clinic. Within the article, they provide an overview of the history of pharmacogenomics (PGx), and then discuss the current state of diagnostic testing and clinical implementation of PGx. Within these latter two sections, Relling and Evans cover both the progress made and the difficulties that still exist with testing and then implementing PGx associations.

Relling and Evans bring up several interesting points in their review. With the falling cost of whole-genome sequencing, it is possible that in the near future, every individual will have their germline genome sequenced early in life. Relling and Evans suggest that there should therefore be a shift away from debate about whether a patient should be tested for genetic variants, and efforts focused instead on providing clinicians with informative guidelines on how to integrate genetic information into prescribing. They also highlight the fact that 7% of FDA-approved medications are affected by actionable pharmacogenes (as defined by the Clinical Pharmacogenetics Implementation Consortium (CPIC)), but that these drugs make up 18% of prescriptions within the United States; this data provides an incentive to improve clinical implementation of PGx. The authors also note the importance of considering multiple variants across one or more genes when analyzing PGx associations, as well as the growing importance and challenges of rare variants. In addition to these particular points of interest, the article also provides an excellent overview on the barriers to clinical implementation, and the complexity of determining the clinical actionability of gene-drug associations.

Read the article:

Pharmacogenomics in the clinic
Relling MV, Evans WE
Nature. 2015 Oct 15. 526(7573):343-50. doi: 10.1038/nature15817

Tuesday, October 13, 2015

Sequence to Medical Phenotypes, a Framework for Interpretation, Published in PLoS Genetics

As the cost of whole genome sequencing plummets and becomes more attractive for widespread application, utility depends on identifying and understanding the importance of specific genetic variants in disease risk and drug response. While tools do exist for interpretation of variants and for predicting phenotypes of novel variation, few are publicly available and are not integrated with each other. An open source framework for the interpretation of these data is presented in “Sequence to Medical Phenotypes: A Framework for Interpretation of Human Whole Genome DNA Sequence Data,” published in PLoS Genetics on October 8. The Sequence to Medical Phenotypes (STMP) framework integrates existing tools, including PharmGKB, for interpretation of variants related to Mendelian disease and drug response. It is customizable and includes both coding and noncoding variation. Its ability to identify clinically actionable and disease-causing variants has been validated in both large sets of unrelated individuals and in father-mother-child trios. It can also be used for genetic risk predictions and drug response predictions for an individual with exome, targeted resequencing, or whole genome DNA sequence data.

The STMP framework is available on the Ashley lab website:

Monday, October 12, 2015

PharmGKB succinylcholine PK/PD pathway published in Pharmacogenetics and Genomics

Succinylcholine (SCH) is a depolarizing neuromuscular blocking agent with a rapid onset of action and short half-life. SCH is commonly used in medical procedures requiring short-term skeletal muscle paralysis, such as intubation during surgery, or emergency medical procedures. The “PharmGKB summary: succinylcholine pathway, PK/PD” has been published in Pharmacogenetics and Genomics. The pathway summary describes the pharmacokinetic and pharmacodynamic pathways of SCH, and adverse reactions to SCH that are associated with variants in the genes BCHE, RYR1, and CACNA1S, as well as in patients with diagnosed with Duchenne or Becker muscular dystrophy. 

View the interactive online version of the pathway here.

See all pathways on PharmGKB.

Saturday, October 10, 2015

Successful implementation of widespread pharmacogenetic testing discussed this week in The Atlantic

An article this week in The Atlantic presents the story of widespread testing for HLA genotypes in some Southeast Asian countries. Simple pharmacogenetic ID cards are issued to inform physicians of a patient’s risk for developing Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) hypersensitivity reactions if prescribed carbamazepine, allopurinol, abacavir, and other drugs. Despite a drop in the incidence of SJS as a result of the cards, better integration with electronic medical records is needed if cases are to be eliminated entirely.

This type of translation of pharmacogenetic research to improve patient outcomes is the goal of the PharmacogenomicsResearch Network (PGRN), supported by the NIH since 2000 under the leadership of Dr. Rochelle Long. Specific PGRN groups address questions ranging from basic science to clinical trials and implementation. In 2009, the Clinical Pharmacogenomics Implementation Consortium (CPIC), led by Dr. Mary Relling of St. Jude Children’s Research Hospital and Dr. Teri Klein of PharmGKB, was established to develop guidelines for and to address barriers to implementation of pharmacogenetic research. The CPIC guidelines for testing of HLA variants in relation to carbamazepine (HLA-B*15:02), allopurinol (HLA-B*58:01), and abacavir (HLA-B:57:01) treatment were published in Clinical Pharmacology and Therapeutics. Each guideline summarizes the relationship of specific HLA variants with hypersensitivity reactions to each drug and recommendations of how to alter care in response. All CPIC guidelines are freely available to the public.

Friday, October 9, 2015

July/August SNPits Summary

The July/August issue of UF Health Personalized Medicine Program's e-newsletter, SNPits, reviews a recent article in the Journal of the American Medical Informatics Association focused on genomic information in the electronic health record (EHR).  The authors of the study looked at how EHRs currently display genomic and genetic information, and how to optimize and improve upon it.  They concluded that the way that genomic information is stored and displayed affects the usefulness of the information, and made several recommendations, including development of clinical decision support (CDS) for genetic results.  Read more.

Wednesday, October 7, 2015

PharmGKB welcomes Alie Fohner to the team

We are pleased to welcome scientific curator Alison (Alie) Fohner to the PharmGKB team. Alie recently earned her PhD in Public Health Genetics at the University of Washington, where she worked with the Pharmacogenomics Research Network group that focuses on rural and underserved populations. Her dissertation included an analysis of genetic and environmental drivers of variation in cytochrome P450 expression in Alaska Native people, and a recommendation for reconciling conflicting ethical and statistical demands in conducting research with historically marginalized populations.  She is excited to be starting with PharmGKB, 10 years after attending a lecture by Russ Altman that inspired her interest in pharmacogenetics, and to be back at Stanford, where she received both a BS and MS in Biology.

Tuesday, October 6, 2015

New CPIC Guideline- UGT1A1 and atazanavir

Guidelines regarding the use of pharmacogenetic tests of UGT1A1 for atazanavir prescribing decisions have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Atazanavir is an antiretroviral protease inhibitor administered to patients infected with the human immunodeficiency virus (HIV). Atazanavir, often co-administered with low-dose ritonavir (atazanavir/r), specifically inhibits UGT1A1-mediated glucoronidation of bilirubin, leading to elevations in concentrations of plasma indirect bilirubin (hyperbilirubinemia). The resulting hyperbilirubinemia is not indicative of hepatic injury, but may result in jaundice in patients with genetic variants that negatively impact UGT1A1 function. Patient stigma due to jaundice may be of particular concern to individuals whose line of work requires them to interact frequently with the public, and may also cause individuals with visible jaundice to prematurely discontinue atazanavir. 

In the newly published guidelines, CPIC recommends advising patients with two decreased function UGT1A1 alleles about their increased chances of developing jaundice if prescribed atazanavir/r. The CPIC recommendations suggest that clinicians avoid prescribing atazanavir to such individuals, unless a patient does not consider jaundice to be a concern, or unless a strong argument exists in favor of prescribing atazanavir.  For patients carrying one, or no decreased function UGT1A1 alleles, CPIC deems the likelihood of bilirubin-related discontinuation of atazanavir to be low, and very low, respectively. 

For details, see the CPIC guideline on PharmGKB.

Tuesday, September 22, 2015

Very Important Pharmacogene: RYR1

The new Very Important Pharmacogene (VIP) Summary of RYR1 describes important pharmacogenetic associations as well as disease associations with variants in RYR1. RYR1 encodes a single sub-unit of the ryanodine receptor isoform 1 (RYR1), the predominant ryanodine receptor isoform of skeletal muscle. RYR1 is a calcium channel of the sarcoplasmic reticulum of muscle cells (and endoplasmic reticulum in non-muscle cells) and is critical to excitation-contraction coupling, the process by which an electrical signal is translated into a muscle contraction. RYR1 is the primary locus for malignant hyperthermia susceptibility (MHS), a potentially fatal pharmacogenetic condition triggered by volatile anesthetics, alone or in combination with a depolarizing neuromuscular blocking agent, such as succinylcholine. There is limited evidence that variants in RYR1 may also be associated with statin-induced myopathies. The VIP summary also discusses how advances in sequencing have improved MHS diagnoses in otherwise healthy individuals. 

Read the VIP summary below:

Saturday, September 19, 2015

Precision Medicine Initiative Working Group Releases Report

The Precision Medicine Initiative (PMI) Working Group of the Advisory Committee to the (NIH) Director (ACD) has recently presented a detailed report to the ACD with recommendations on how to a build and manage a diverse research cohort of 1 million people for the PMI. The report discusses a framework for policies affecting patient recruitment, specimen collection and storage, technology infrastructure, operations, privacy, security and sharing of data between researchers and cohort participants. A notable recommendation is the use of arrays that prioritize the inclusion of known pharmacogenetic variants.  The report also recommends including anyone who is willing to participate in the PMI, and emphasizes the importance of having a diverse cohort that is representative of the general population of the United States.The ACD unanimously agreed to accept the PMI Working Group’s report, and according to Dr. Russ Altman, a member of the ACD, "Direct participation is clearly the alternative in this age of consumer empowerment.” 

Read more about the PMI Working Group’s report, including an interview with Dr. Russ Altman with GenomeWeb below:

Wednesday, September 2, 2015

Electronic Medical Records and Genomics (eMERGE) Network to receive more than $48 million from the National Institutes of Health

NIH grants totaling more than $48 million dollars have been awarded to support phase III of the eMERGE network program. eMERGE is a consortium of research institutions focused on linking genome-wide genotyping or sequencing data with patient electronic medical records (EMRs) in order to improve patient care. eMERGE PGx, a partnership between eMERGE and the Pharmacogenomics Research Network (PGRN) has successfully deployed a next-generation sequencing platform called PGRN-seq to sequence very important pharmacogenes in patients across eMERGE sites with a goal of integrating pharmacogenetic genotypes into electronic health records, as well as the associated clinical decision support. Among the awardees of the NIH grants were researchers at Vanderbilt University, an eMERGE site, led by Dan Roden and Joshua Denny. The group will investigate the impact of rare variants on health and drug response as well as expand the Pharmacogenomics Research for Enhanced Decision in Care and Treatment (PREDICT) pipeline. 

Read more about the NIH awards here:

Read more about the eMERGE Network here:

Read more about eMERGE PGx here:

Thursday, August 27, 2015

PharmGKB Pathway Peginterferon-α published in Pharmacogenetics and Genomics

The PharmGKB summary:  peginterferon-α pathway has been published in the Pharmacogenetics and Genomics Journal. Peginterferon-α (pegylated interferon-α or PEG-IFN-α) is an antiviral drug used to treat chronic hepatitis C virus (HCV) infection. The PharmGKB review summarizes the pharmacokinetics and pharmacodynamics of peginterferon-α and also discusses genetic variations around the IFNL3 locus (formerly known as IL28B) affecting the viral clearance and clinical responses to peginterferon-α based therapy.
Find out more...
View interactive Peginterferon-α pathway on PharmGKB.

Read our new publication:
Pharmacogenet Genomics. 2015 Sep; 25(9):465-74
Shuldiner SR, Gong L, Muir AJ, Altman RB, Klein TE. 
PMID: 26111151

View all pathways on PharmGKB.

Tuesday, August 4, 2015

The National Institutes of Health Awards $14 million to Stanford Researchers for Precision Medicine Projects

The National Institute for General Medical Sciences (NIGMS) has awarded a $10 million grant to Dr. Teri Klein and Dr. Russ Altman to continue and expand the Pharmacogenomics Knowledgebase (PharmGKB), the premier resource for curated knowledge about the impact of human genetic variation on drug responses. In addition, Dr. Klein and Dr. Mary Relling, PharmD, Chair of Pharmaceutical Sciences at St. Jude Children’s Hospital were also awarded a $4 million grant from the NIGMS and National Human Genome Research Institute (NHGRI) to fund the Clinical Pharmacogenetics Implementation Consortium (CPIC). CPIC publishes guidelines that enable the translation of genetic tests into actionable prescribing decisions for specific drugs.

Read the press release from the Stanford Medicine News Center below:

Monday, July 27, 2015

Remembering PharmGKB Alum Steve Lin

The PharmGKB team is deeply saddened by news of the recent passing of Steve Lin.  Steve was one of the first developers at PharmGKB and he helped to create the initial version of the resource.  He will be greatly missed.  Our sincere condolences go to his family in their time of sorrow.

Friday, June 26, 2015

Medication Safety Code Initiative Looking for Survey Participants

The Medication Safety Code (MSC) Initiative ( aims to improve the portability of pharmacogenetic data by enabling patients to carry information about their pharmacogenetic test results with them so it is available at the point of care.  The MSC system utilizes a QR (2D) barcode that can be decoded using a standard mobile device with access to the internet.

The MSC is conducting a survey ( to help identify the essential pieces of information that need to be included in the system.  We estimate that it will take 10-15 minutes to complete the survey.  The first 10 respondents will receive a $17 / 15€ Amazon gift card.

Please consider responding to this survey by July 19th, 2015.  All information will be kept strictly confidential  and used only for the purposes of research for this project.  If you have any questions or if you experience technical difficulties accessing or submitting the survey please contact

Friday, June 12, 2015

CPIC Guideline Update for Allopurinol and HLA-B*58:01 Published

The 2015 update of CPIC guideline for allopurinol and HLA-B*58:01 has been published in Clinical Pharmacology and Therapeutics. CPIC extensively reviewed the recent literature and concluded that the dosing recommendations provided in the 2013 CPIC guideline have not changed.

The 2015 update includes the following additions:
  • Updated evidence linking HLA-B*58:01 to phenotype (Supplemental Table S3).
  • Added figures depicting clinical implementation workflow for EHR and Point of Care Clinical Decision Support (Supplemental Figures S1 and S2)

View the interactive CPIC allopurinol dosing guideline based on HLA-B*58:01, with the available full update and original published guidelines.

Thursday, June 11, 2015

March/April SNPits Summary

In the March/April issue of UF Health Personalized Medicine Program's e-newsletter, SNPits, a recent study in the Lancet supports the benefit of pharmacogenomic testing for warfarin dosing is reviewed.  The authors found that those patients with warfarin-sensitive genotypes were more likely to be over-anticoagulated in the first 90 days.  Additionally, there were more overt bleeding events for patients with warfarin-sensitive genotypes.  Read more.

Wednesday, June 10, 2015

Annotated Health Canada product monographs now available on PharmGKB

PharmGKB now has annotated drug labels (referred to as product monographs) available from Health Canada/Santé Canada (HCSC).

PDF copies of the product monographs were sourced from HCSC's Drug Product Database (DPD). As with the annotated U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and Pharmaceutical and Medical Devices Agency, Japan (PMDA) drug labels, HCSC monographs are given a PGx level of evidence, and a PDF copy of the product monograph with PGx information highlighted is available for each annotated monograph.

HCSC product monographs were selected for examination for PGx information based on the FDA's Table of Pharmacogenomic Biomarkers in Drug Labeling, as well as any EMA labels with PGx information that PharmGKB has curated.

It is possible that there are other HCSC product monographs that contain PGx information, and PharmGKB welcomes any feedback regarding PGx information within HCSC product monographs or labels from other medicine agencies around the world.

See a list of product monographs available on PharmGKB:
HCSC product monographs on PharmGKB

Monday, June 8, 2015

NIGMS announces funding changes for PGRN

NIGMS announces the transition of pharmacogenomics research from set-aside funding to regular competition.  The FOA for Research Centers for Pharmacogenomics in Precision Medicine (P50) is discontinued for 2015 and 2016.  Starting in mid-July, any investigator interested in PGx can join the Pharmacogenomics Research Network through the PGRN website. 

Monday, May 18, 2015

PharmGKB efavirenz pharmacokinetic pathway published in Pharmacogenetics and Genomics

The PharmGKB summary describing the efavirenz (EFV) pharmacokinetic pathway, and the pharmacogenetic variants that affect EFV pharmacokinetics has been published by Pharmacogenetics & Genomics

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor that is used as part of a highly active anti-retroviral therapy (ART) regimen (HAART) against HIV-1 infection. The primary route of EFV metabolism is through CYP2B6 to 8-hydroxyefavirenz (8-hydroxy-EFV).  In vitro studies using human liver microsomes show that there is considerable variability in the formation rate of 8-hydroxy-EFV between samples and genetic variants in CYP2B6 are likely major contributors to this variability. There is also evidence that CYP3A4, CYP3A5, CYP1A2 and CYP2A6 also play minor roles in this xenometabolic step. 

View the interactive online version of the PharmGKB summary: Efavirenz pathway, pharmacokinetics (PK) here and on Pubmed.

View all pathways on PharmGKB.