ArticleJournal of translational medicine2025
Polygenic and pharmacogenomic contributions to medication dosing: a real-world longitudinal biobank study.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- preSCRIPT: Large-scale prescription search and annotation engine for pharmacogenomic studies.Pharmacological reports : PR · 2026Article
- Pharmacogenetic Associations with Statin Regimen Modification, Intolerance, and Adverse Outcomes in Coronary Artery Disease Patients.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Translating the effect of dual lipid reduction with PCSK9 inhibitors on a mechanical vascular instrumental biomarker in familial hypercholesterolemia subjects.Journal of translational medicine · 2025Observational
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7 authors.
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Abstract
backgroundUnderstanding interindividual variability in medication dosing is central to precision medicine. Despite significant pharmacogenomic (PGx) insights into key biological pathways influencing drug response, the polygenic contribution to dose variability and the potential of electronic health records for maintenance dose estimation remain largely unexplored.
methodsWe leveraged longitudinal drug purchase data linked to the Estonian Biobank (N = 212,000) to derive individual-level daily doses per purchase as well as median and maximum doses as consolidated metrics across purchases for cardiovascular and psychiatric drugs: statins, warfarin, metoprolol, antidepressants, and antipsychotics. Associations with polygenic scores (PGSs) for 16 traits were assessed using linear mixed models and multivariable regression with a forward stepwise approach. Genome-wide association studies (GWAS) were followed by gene set enrichment analyses for known PGx genes.
resultsSample sizes ranged from 684 (antipsychotics) to 20,642 (statins), with median doses reflecting typical maintenance doses. Trait-specific PGSs were significant for the daily dose of statins (coronary heart disease PGS, β = 0.02, P = 5.9 × 10
conclusionsThese findings illustrate the feasibility and value of leveraging real-world electronic health records to derive pharmacologically meaningful medication dosing phenotypes. Both polygenic and pharmacogenomic signals contribute to dose variability, underscoring their potential utility in personalized prescribing strategies.
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