Friday, June 29, 2018

Curators' Favorite Papers

The growing number of individuals using direct to consumer (DTC) genetic tests has also led to an increase in physicians counseling patients on their results. In an effort to reveal the perspectives of physicians who receive these “unsolicited genomic results” (UGR), the Electronic Medical Records and Genomics (eMERGE) Network has conducted a survey, published in Genetics in Medicine (Physicians’ perspectives on receiving unsolicited genomic results) in which they ask physicians about their perspectives on the actionability of positive test results, what they believe their responsibilities are for UGRs, the impact of UGRs on patients and clinical workflow, and the the process and support involved in returning results. The 25 participants were selected because of their extensive experience as primary care physicians, pediatricians, cardiologists, or oncologists. The primary concern of physicians was that only actionable results should be returned to patients, and that any follow-up should include clinical decision support and be evidence-based. Additional concerns included the additional time that would need to be set aside to integrate results into clinical workflow, increased patient anxiety and confusion, and whose responsibility it was to “own” genetic test results. 

Pharmacogenetic algorithms have been demonstrated to improve the dosing of essential life-saving medications such as warfarin, as well as to reduce the incidence of adverse effects. However, dosing algorithms and recommendations often include genetic variants that come from cohorts of individuals who are predominantly of European descent and largely overlook variants that are prevalent in other populations. The authors of a new editorial in the journal Pharmacogenomics (Preventing the exacerbation of health disparities by iatrogenic pharmacogenomic applications: lessons from warfarin) review studies investigating warfarin dosing in underrepresented and admixed populations in Puerto Rico, Brazil, and the United States. In addition to noting the importance of cataloging variants in diverse populations, the authors also stress the complications that may arise when self-reported color or race categories, which vary by country, are used as proxies to infer the presence of pharmacogenetic variants. The authors also note that the 2017 update of the Clinical Pharmacogenetic Implementation Consortium (CPIC) for Warfarin Dosing reflects some of these new findings and it includes self-reported ancestry and variants that are more commonly found in African-American patients in the dosing algorithm.

You can find more information about pharmacogenetic guided dosing for warfarin on as well as on the PharmGKB’s annotation of the CPIC Guideline update for warfarin and CYP2C9, VKORC1, CYP4F2 and the single nucleotide polymorphism, rs12777823.