Scientific Poster Session III - Encore

Encore Presentations
  Monday, October 14, 2024
  01:00 PM–02:30 PM

Abstract

Historically, the clinical genomics (CGx) and pharmacogenomics (PGx) domains have remained largely distinct. CGx assesses genetic determinants/predictors of disease risk/pathology, while PGx evaluates genes associated with pharmacokinetics/pharmacodynamics. However, there are notable examples of CGx/PGx pleiotropy, wherein a hereditary condition confers a potential for medication-related adverse events and/or inefficacy. While several papers have explored disease associations of commonly tested PGx variants, we are unaware of any literature evaluating PGx implications of commonly tested CGx conditions.

To address this gap, we performed review of genes reported on the American College of Medical Genetics’ (ACMG) Secondary Findings v3.2 list (SF v3.2) to identify those with pharmacotherapy implications. For each gene, we searched two common clinical sources of genomic information: GeneReviews (“Agents/Circumstances to Avoid” section) and PharmGKB (“Drug Label Annotation” and “Variant Annotation” sections). Targeted therapies for specific germline/somatic mutations were excluded. Interactions were rated on a 1-4 scale: Level 1 indicates CPIC/FDA-driven recommendations, Level 2 indicates a reasonable likelihood of clinically significant interactions, Level 3 indicates emerging evidence for an interaction but no recommendations, and Level 4 indicates no/weak interactions. We defined Level 1 or 2 as the threshold for clinical actionability.

Of the 81 genes reviewed, 30 (37%) had Level 1 or Level 2 interactions. PharmGKB identified 3/4 (75%) Level 1 interactions and 5/26 (19%) Level 2 interactions. GeneReviews identified 3/4 (30%) Level 1 interactions and 19/26 (73%) Level 2 interactions. Neither source identified 7/30 (23%) Level 1 or Level 2 interactions.

As clinical practice continues to move towards broad preemptive genetic testing, practitioners must be aware of both CGx and PGx implications of genetic findings. Our results emphasize a need for greater research on pleiotropic CGx/PGx genetic effects, highlight the need for greater collaboration between pharmacists and clinical genetics professionals, and imply a potentially broader scope of practice for PGx pharmacists.

Presenting Author

Josiah Allen PharmD
St. Elizabeth Healthcare

Authors

Jordan Brady MS,CGC
St. Elizabeth Healthcare

Benjamin Duong PharmD
Nemours Children's Health