Andrea Gaedigk, PhD, Director of the Pharmacogenetics Core Laboratory at Children’s Mercy Hospital Kansas City and the PI of the PharmVar Consortium, and Neil Miller, Director of Bioinformatics, Center for Pediatric Genomic Medicine at Children’s Mercy Hospital Kansas City
Understanding individual response to drugs plays a central role in precision medicine. As pharmacogenetic testing becomes more and more prevalent, it’s crucial that the clinical and research communities have a global resource that provides nomenclature for defining and reporting genetic variants that help guide drug choice and dosing in adults and children. This resource also needs to keep up with the new era of genomics and the rate at which we’re finding new allelic variants.
After more than 15 years, the Human Cytochrome P450 Allele Nomenclature website, which has been the established authority for issuing and maintaining allele designations, has been transitioned to the Pharmacogene Variation (PharmVar) Consortium. This new home will serve as a centralized “Next-Generation” Pharmacogene Variation data repository and support the continued development of pharmacogene nomenclature.
The first version of the PharmVar database will be launched by the end of March and will contain the high-priority CYP2C9, CYP2C19 and CYP2D6 genes, while other P450 genes will be transferred into the PharmVar database soon thereafter. One particular feature of the new database is easy switching between different reference sequences making finding positions of sequence variants a breeze. The database will eventually also feature customizable tables showing alleles and regions of interest, an API for programmatic access, sequence alignments, and user options of downloading variant sequences.
Anyone in academia, industry or clinical test labs can submit new allele definitions. Data will be included in the database after review by a group of experts. This is truly a community process involving gene experts from around the world that will help provide new definitions and high-quality data for everyone to use.
In addition to a transparent submission and review process, the PharmVar database will assign unique version numbers to haplotype definitions, genes and database releases to enable robust tracking of nomenclature data and simplifying the task of determining the exact allele definitions used in a particular analysis or described in a publication.
It’s important for the community to have one place that keeps track of all these variations because it allows us to standardize the names we use to describe the variants and ensure we are all speaking the same language.
Pharmacogenomics is positioned at the leading edge of genomic medicine, and there have been huge advances made in using DNA testing to guide drug choice and dosage. This individualized approach allows for treatment to be customized to a particular patient instead of the one-size-fits all dosing model. Pharmacogenetic testing is increasingly used at our institution and many others to guide treatment for behavioral disorders such as ADHD. The next frontier is using genomics in everyday health care for every patient.
Right now, a lot of actionable data is sitting in silos in hospitals and data centers around the world, because we are sure many of our peers just haven’t found a home for it yet. PharmVar hopes to address this by establishing one place to keep track of variation. Providing a systematic catalog is a key part to successful implementation of pharmacogenetics into the clinic, and we hope this resource will have an impact on individualized patient care and health outcomes.
The Hub team