ClinGen, CPIC and PharmGKB Partnership 

ClinGen, CPIC and PharmGKB Partnership 

I. Introduction

ClinGen, CPIC and PharmGKB, all NIH-based efforts, have formed a critical partnership to expand ClinGen’s valuable clinical genetics resource to include pharmacogenetics (PGx).  CPIC and PharmGKB are two main resources for the PGx research and implementation communities. This partnership provides the opportunity to characterize and disseminate the clinical relevance of pharmacogenetic variation based on expert, manually curated information created through transparent, documented Standard Operating Procedures (SOPs). 

II. The ClinGen-CPIC-PharmGKB Partnership

ClinGen’s Expert Panels review gene-disease relationships, but do not include gene-drug relationships, while CPIC and PharmGKB focus on gene-drug and variant-drug associations. CPIC provides evidence-based clinical practice guidelines for pharmacogenetics implementation, and assigns clinical actionability to gene/drug pairs. PharmGKB provides expertly curated variant-drug phenotype summaries based on peer-reviewed publications, including associations for which the level of evidence may not yet reach the requirement for an implementation guideline. 

ClinGen has partnered with CPIC and PharmGKB to bring pharmacogenetics knowledge to ClinGen. This knowledge is represented at the gene level on the ClinGen website, displaying PGx relationships alongside validation, dosage and actionability curations. PharmGKB also represents disease phenotypes using standardized vocabularies (e.g. SNOMED) linked to genes and variants, and will represent ClinGen’s clinical relevance for genes and variants associated with disease on the PharmGKB website for dissemination to the PGx community.

ClinGen, CPIC and PharmGKB are aligned and play a critical role in the growing data sharing movement within the clinical genetics community, with CPIC and PharmGKB focusing on pharmacogenetics, an area not previously included in the ClinGen effort.  ClinGen relies on CPIC and PharmGKB as sources for expertly curated pharmacogenetic knowledge.

III. Details about ClinGen, CPIC and PharmGKB

The Clinical Genome Resource (ClinGen)

  • ClinGen creates authoritative central resources that define the clinical relevance of genes and variants for use in precision medicine and research.
  • ClinGen is primarily funded by the National Human Genome Research Institute (NHGRI), through the following three grants: U41HG006834, U41HG009649, U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the following three grants: U24HD093483, U24HD093486, U24HD093487.
  • ClinGen Goals:
    • Share genomic and phenotypic data between clinicians, researchers, and patients through centralized and federated databases for clinical and research use.
    • Develop and implement standards to support clinical annotation and interpretation of genes and variants.
    • Develop data standards, software infrastructure and computational approaches to enable curation at scale and facilitate integration into healthcare delivery.
    • Enhance and accelerate expert review of the clinical relevance of genes and variants.
    • Disseminate and integrate ClinGen knowledge and resources to the broader community.

The Clinical Pharmacogenetics Implementation Consortium (CPIC)

  • CPIC is an international consortium of scientists and clinicians which facilitates the use of pharmacogenetic tests for patient care by creating freely available, peer-reviewed and evidence-based detailed gene/drug clinical practice guidelines following the rigorous National Academy of Medicine's (formerly Institute of Medicine’s) standards for writing trustworthy clinical practice guidelines.
  • CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, assuming that genetic testing is becoming more widespread.
  • CPIC focuses on germline pharmacogenetics
  • CPIC is funded by the National Human Genome Research Institute (NHGRI) through grant U24HG010135
  • CPIC highlights:
    • Freely-available at
    • Updated regularly
    • Assigns clinical actionability levels to gene/drug pairs
    • Contain links to tables that can be used at clinical implementation sites to facilitate integration into electronic health care records
    • Indexed in PubMed as clinical guidelines
    • Endorsed/supported by professional societies (ASHP, ASCPT, CAP)
    • Adheres to standard formats: standardized terms for allele function and phenotypes
    • Has systems for grading levels of evidence, for assigning function to alleles, for assigning phenotypes to genotypes, and assigning strengths to each prescribing recommendation

The Pharmacogenomics Knowledge Base (PharmGKB)

  • The mission of PharmGKB is to collect, curate, integrate and disseminate knowledge about how human genetic variation influences drug response.
  • PharmGKB is the largest publicly available resource for pharmacogenomics (PGx) discovery and implementation.
  • PharmGKB Clinical Annotations summarize all of PharmGKB’s annotations of published evidence for the relationship between a particular genetic variant and a medication. Clinical Annotations are created by PGx experts based on manual curation of the published evidence and given a rating depending on the amount and the quality of that evidence.
  • PharmGKB is funded by the National Human Genome Research Institute (NHGRI) and the National Institute of Child Health and Human Development (NICHD) through grant U24 HG010615. 
  • PharmGKB highlights:
    • Manual curation of peer-reviewed PGx literature, drug labels and prescribing guidelines.
    • Annotations created using standard data formats and following standard operating procedures for assessing variant-drug phenotype associations
    • All supporting evidence (PMIDs) is provided with annotations
    • Systematic ratings for the level of evidence for annotations
    • Annotations are continually updated as new evidence is curated
    • Use of existing standardized vocabularies for drugs (including RxNorm), drug and disease phenotypes (including SNOMED), genes (HGNC) and variants (including dbSNP rsIDs, genomic coordinates, star allele nomenclature)
    • All PharmGKB data and resources can be freely downloaded and used under the terms of a Creative Commons License