Genomics-first association of pharmacogenomic risk phenotypes with adverse drug reactions in a healthcare-based population.
TL;DR
A portion of population ADR burden could possibly have been prevented through PGx-guided therapy and a portion of population ADR burden could possibly have been prevented through PGx-guided therapy.
Abstract
Purpose
Pharmacogenomic (PGx) variation affects drug metabolism and adverse drug reaction (ADR) risk. While the Clinical Pharmacogenetics Implementation Consortium (CPIC) lists 573 actionable gene-drug pairs, large-scale evaluation of PGx-related ADRs remains limited. We performed a retrospective genomic-first analysis on genetic and electronic health record (EHR) data to assess PGx impact on ADR risk.
Methods
We analyzed 226,053 individuals in the Geisinger MyCode cohort for 58 CPIC high-risk gene-drug associations spanning 11 genes. Genetic findings were linked to EHR allergy and medication discontinuation records.
Results
Most individuals (211,920/226,053, 93.7%) had at least one actionable PGx phenotype and 44.4% (100,402/226,053) had an actionable phenotype conferring ADR risk and were prescribed a relevant medication. As individuals accumulate medication exposures, ADR incidence increases (Pearson's correlation=0.50, P<0.001). Individuals with risk phenotypes were more likely to have a documented allergy or ADR-related medication discontinuation (P<0.001, OR=1.4), and 3.9% (8,913/226,053) exhibited an ADR associated with personal PGx risk. We observed 36,194 ADRs across 27,546 individuals (12.2% of cohort); 10,719/36,194 (29.6%) occurred in individuals with relevant PGx phenotypes.
Conclusion
Individuals exposed to more medications exhibit increased ADR rates. PGx further compounds ADR risk, and a portion of population ADR burden could possibly have been prevented through PGx-guided therapy.