Abstract
Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug-metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug-metabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (http://bbmri.researchlumc.nl/atlas/).
Original language | English |
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Pages (from-to) | 110-117 |
Number of pages | 8 |
Journal | Nature Medicine |
Volume | 26 |
Issue number | 1 |
Early online date | 13 Jan 2020 |
DOIs | |
Publication status | Published - Jan 2020 |
Funding
both within the framework of the Netherlands Genomics Initiative (NGI)/NWO (to A.M.J.M.v.d.M.) and by the FP7 EU project EUROHEADPAIN (grant no. 602633) (to A.M.J.M.v.d.M. and G.M.T.). NEO: the authors of the NEO study thank all individuals who participated, all participating general practitioners for inviting eligible participants and all research nurses for collection of the data. We thank the NEO study group—P. van Beelen, P. Noordijk and I. de Jonge—for coordination, laboratory and data management of the study. Genotyping in the NEO study was supported by Centre National de Génotypage (Paris, France), headed by J.-F. Deleuze. This study was supported by the participating departments, the Division and the Board of Directors of Leiden University Medical Center and by Leiden University, Research Profile Area Vascular and Regenerative Medicine. The study was also supported by the Netherlands Cardiovascular Research Initiative: an initiative with the support of the Dutch Heart Foundation (no. CVON2014-02 ENERGISE).
Funders | Funder number |
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Centre National de Génotypage | |
Netherlands Genomics Initiative | |
Northern Gulf Institute | |
Seventh Framework Programme | 602633 |
Universiteit Leiden | |
Hartstichting | CVON2014-02 |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
Leids Universitair Medisch Centrum |
Cohort Studies
- Netherlands Twin Register (NTR)