ArticleClinical and translational science2022
Leveraging large observational studies to discover genetic determinants of drug concentrations: A proof-of-concept study.
Article in Clinical and translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- CYP2D6 Metabolizer Status and Mortality in Metoprolol Users.Clinical and translational science · 2026Article
- A Study Of the effect of Sex on drug dosing, concentrations, and pharmacogenomics in the Montreal Heart Institute Hospital Cohort (SOS-PGx): methodology and research progress.European journal of clinical pharmacology · 2025Article
- Impact of amiodarone use on metoprolol concentrations, α-OH-metoprolol concentrations, metoprolol dosing and heart rate: A cross-sectional study.Pharmacology research & perspectives · 2023Article
- Females present higher dose-adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males.Clinical and translational science · 2023Article
- An association study of ABCG2 rs2231142 on the concentrations of allopurinol and its metabolites.Clinical and translational science · 2022Article
- Leveraging large observational studies to discover genetic determinants of drug concentrations: A proof-of-concept study.Clinical and translational science · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Large, observational genetic studies are commonly used to identify genetic factors associated with diseases and disease-related traits. Such cohorts have not been commonly used to identify genetic predictors of drug dosing or concentrations, perhaps because of the heterogeneity in drug dosing and formulation, and the random timing of blood sampling. We hypothesized that large sample sizes relative to traditional pharmacokinetic studies would compensate for this variability and enable the identification of pharmacogenetic predictors of drug concentrations. We performed a cross-sectional, proof-of-concept association study to replicate the well-established association between metoprolol concentrations and CYP2D6 genotype-inferred metabolizer phenotypes in participants from the Montreal Heart Institute Hospital Cohort undergoing metoprolol therapy. Plasma concentrations of metoprolol and α-hydroxymetoprolol (α-OH-metoprolol) were measured in samples collected randomly regarding the previous metoprolol dose. A total of 999 individuals were included. The metoprolol daily dose ranged from 6.25 to 400 mg (mean 84.3 ± 57.1 mg). CYP2D6-inferred phenotype was significantly associated with both metoprolol and α-OH-metoprolol in unadjusted and adjusted models (all p < 10
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