Wednesday, June 29, 2016

Wall Street Journal Discusses Predispositional Personal Genome Sequencing, PGx

A recent article by Laura Landro in the Wall Street Journal titled “Why Knowing Your Genetic Data Can Be a Tricky Proposition” discusses the benefits and complications of Predisposition Personal Genome Sequencing (PPGS) and the Personal Genome Sequencing Outcomes, or PeopleSeq consortium. PPGS is preemptive genome sequencing of apparently healthy patients, which contrasts with genome sequencing  for diagnosis of genetic disease. The article highlights the efforts of private companies, health care systems and academic research centers, some of which include members of the Clinical Pharmacogenetics Implementation Consortium (CPIC) that conduct PPGS in healthy patients. Although it emphasizes how PPGS may help patients discover genetic pre-disposition to disease, many institutions, including those that collaborated as part of the PeopleSeq consortium, returned pharmacogenomics results for health records or to patients if requested.  Of 258 adults surveyed from the three PeopleSeq sites (Harvard Personal Genome Project, Illumina Understand Your Genome program and Mount Sinai HealthSeq), 81% said it was “very” or “somewhat important” to learn about personal response to medications. In addition, 99 and 98% had a “personal interest in genetics in general” and “curiosity about my genetic make-up”, respectively, while “92% had a desire to participate in research to help others”. The favorable attitude of many participants towards genome sequencing and pharmacogenomics, demonstrates a growing understanding and awareness of genomics, which is an encouraging sign for genomics and pharmacogenomics research.

Friday, June 10, 2016

Congratulations to Dr. Rochelle Long in her new role at NIGMS

The PharmGKB team congratulates Dr. Rochelle Long, our program officer for the past 16 years, in her new role as Director of NIGMS Division of Pharmacology, Physiology, and Biological Chemistry.  Dr. Long’s vision, leadership, dedication, friendship and support have been instrumental in elevating and maturing the field of pharmacogenomics. Her friends and colleagues describe her by the words below:

We wish her great success in her new position, we look forward to her continued leadership, and, impact on and the facilitating of novel science

NIGMS has issued a press release detailing her new appointment.

Wednesday, June 8, 2016

Spring SNPits Summary

The Spring edition of UF Health Personalized Medicine Program's e-newsletter, SNPits is out now. This edition of SNPits summarizes and discusses publications in the American Journal of Health-System Pharmacy, Gastroenterology, and Genetics in Medicine. 

The first publication summary was of a retrospective study that analyzed the pharmacogenetic (PGx) and medication history data from over 20,000 male and female patients of various ethnicities who had been referred to Genelex for pharmacogenetic (PGx) testing. Some patients had genotype information for one CYP gene, while others had genotype information for CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5. The study reports that 93% of the individuals with genotype information for five SNPs were not “normal metabolizers” for at least one CYP isoenzyme, and that older patients were more likely to have potential drug-gene interactions (DGI) or drug-drug-gene interactions (DDGI) as compared to younger patients, likely due to polypharmacy. The authors of the study conclude that the relatively high prevalence of potential and actual DGIs and DDGIs (27.3% of all subjects were found to have at least one physician recommendation to change or consider changing medications due to DGI or DDGI) suggests that PGx testing benefits all patients, and that older patients on multiple drugs are at increased risk for harm. Read the SNPit here. 

The second publication summary was of a study in Dutch patients from 30 hospitals with inflammatory bowel disease (IBD). Thiopurines are standard treatment for IBD and variants in the TPMT gene (TPMT *2, *3A, *3C) are associated with increased hematological adverse reactions (ADRs) such as leukopenia or low platelet counts in patients administered thiopurines. Patients were randomized to receive a standard dose of thiopurines (controls) or TPMT genotype based dosing (intervention). Patients homozygous for the aforementioned TPMT variants received 0-10% of standard dose, and patients heterozygous for those variants received 50% of standard dose. Primary outcomes were the occurrence of a hematological ADR. In a twenty week follow-up the authors found no difference in the proportion of patients with hematological ADRs when comparing between the intervention and control groups (7.4% of the intervention vs 7.9% control; relative risk, 0.93; 95% CI 0.57-1.52). However, when looking exclusively at patients who carried TPMT variants, the proportion of patients that developed ADRs in the intervention was significantly lower (2.6%) as compared to the control group (22.9%) (relative risk, P= 0.11; 95% CI, 0.01-0.85). There was no significant difference in clinical outcome between groups. Read the SNPit here

Finally, the third publication summary is of a position statement from the American College of Medical Genetics Board of Directors regarding direct-to-consumer genetic testing, also known as DTC genetic testing. The publication is a revision statement from the ACMG Board of Directors on the use of DTC genetic testing. The revised position statement recognizes the utility of DTC genetic testing, but cautions that several conditions should be met for DTC genetic testing. Read the SNPit here

Genotype based dosing guidelines for CYP2D6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, and TPMT are available at PharmGKB and CPIC

Friday, June 3, 2016

PGRN meeting at ASHG October 17-18, 2016

The PGRN is hosting a symposium, The Expanding Universe of Pharmacogenomics, right before the ASHG Annual Meeting in Vancouver, Canada on October 17 & 18, 2016.  The symposium is open to all ASHG attendees, PGRN members and others who are interested.

Details and agenda can be found at

Friday, May 27, 2016

NIGMS Request for Information: Approaches for Supporting Team Science in the Biomedical Research Community

The National Institute of General Medical Sciences (NIGMS) has issued a request for information (RFI: Approaches for Supporting Team Science in the Biomedical Research Community) in order to seek input on how best to support team-based scientific research. The NIGMS defines team science as research that requires multiple investigators to answer research questions that cannot be answered by one investigator or a group supported by a multi-PI R01 grants (Notice number: NOT-GM-16-107).

A full description of the RFI is available at:

The responses to the RFI will be accepted through June 17, 2016. Responses may be submitted as text or an attachment in an e-mail to or may be submitted anonymously with a web form ( 

We encourage our scientific community to communicate their thoughts to these important initiatives to NIH. 

Thursday, May 26, 2016

Race and Pharmacogenetics discussed in the New England Journal of Medicine

The authors of a new Perspective in the New England Journal of Medicine (“Will precision medicine move us beyond race?”) focus on the potential pitfalls of using race based categories as proxies for pharmacogenetic variants. Self-identified race may not predict genotype or drug response in individual patients and the use of race as a proxy for ancestry and genetic variants is controversial and problematicAs an example of the power of precision medicine, and specifically pharmacogenetics, Bonham et al. discuss a 2014 lawsuit by the Hawaiian attorney general against the manufacturers of clopidogrel. The lawsuit claims that clopidogrel was marketed and sold to Hawaiians despite well-established studies showing that specific alleles in CYP2C19 (*2 and *3) compromise its efficacy and that those alleles are also known to be common in a significant proportion of Hawaii’s population (East Asian, Native Hawaiian and other Pacific Islanders). Bonham et al. believe that greater cohort diversity in prospective longitudinal drug studies will improve understanding of how genetic variability may affect drug response and safety between and within populations. In addition, they argue that sub-populations that respond best to targeted drug therapies would also benefit from these studies because the studies would provide the necessary evidence of therapeutic efficacy to justify the increased costs of treatment in those groups. Finally, evidence from such studies will be necessary to mobilize training resources for clinicians and health care systems so that they can incorporate pharmacogenetic information into routine dosing and prescribing decisions to ultimately improve treatment.   

More information about CYP2C19, and clopidogrel, including the FDA-approved drug label with annotated pharmacogenetic information can be found on PharmGKB. Dosing guidelines for CYP2C19 and clopidogrel are available on PharmGKB and CPIC

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.