Curators' Favorite Papers

The first paper from Genetics in Medicine by Khoury et al. (From Public Health Genomics to Precision Public Health: a 20-Year Journey) reviews developments in the field of public health genomics over the last twenty years. Public health genomics deals with the “effective and responsible translation of genomic research into population health benefit” through assessment, policy, and assurance. It summarizes current research projects in the field and describes the role of organizations, including the Centers for Disease Control and Prevention (CDC) in the development and implementation of evidence-based guidelines for genetic testing. The authors recognize that genomics cannot be isolated from other determinants of health including behaviors or socioeconomic factors such as housing, education, and access to care and the need for subsequent developments in “precision public health” to integrate genomics data with other health determinants to improve public health outcomes.


Despite the fact that over 100 GPCRs are targeted by approximately 34% of FDA-approved drugs, the frequency of genetic variation of GPCRs is not known according to a study by Hauser et al. from the December issue of Cell (Pharmacogenomics of GPCR Drug Targets). The study evaluates pharmacogenetic (PGx) variation in 108 G-protein coupled receptors (GPCRs) using datasets from the exome aggregation consortium (ExAC) and the 1000 Genomes Project that include over 60,000 individuals and estimates that there is an average of 128 rare and 3.7 common variants per receptor and that 25% of all positions in each GPCR contains a missense variant. In addition approximately 120 of the 60,706 individuals from the dataset harbored loss of function mutations in a GPCR drug target and each GPCR had approximately two duplications and three deletions. The authors support their findings with an analysis of the molecular literature, including data from PharmGKB Clinical Annotations, functional PGx studies of GPCRs on drug response and efficacy and an economic analysis of how incorporation of GPCR PGx could decrease the UKs National Health Service (NHS) financial burden.

PharmCAT commentary in Clinical Pharmacology & Therapeutics

A commentary about the Pharmacogenomics Clinical Annotation Tool (PharmCAT) was recently published in Clinical Pharmacology & Therapeutics.  PharmCAT is developed in a collaboration between the former PGRN Statistical Analysis Resource (P-STAR) and the Pharmacogenomics Knowledgebase (PharmGKB) with input from other groups (click here for a list of participants). PharmCAT will extract PGx variants, beginning with variants in genes with CPIC guideline recommendations, from VCF files, infer diplotypes/genotypes, and generate an interpretation report containing the relevant CPIC recommendations.

In the article, Teri Klein and Marylyn Ritchie highlight challenges in the field and describe the rationale for PharmCAT. The tool's workflow is depicted graphically and the different components are briefly introduced.

For more information about PharmCAT read the complete commentary at Clinical Pharmacology & Therapeutics.