Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug–metabolite atlas

Jun Liu*, Lies Lahousse, Michel G. Nivard, Mariska Bot, Lianmin Chen, Jan Bert van Klinken, Carisha S. Thesing, Marian Beekman, Erik Ben van den Akker, Roderick C. Slieker, Eveline Waterham, Carla J.H. van der Kallen, Irene de Boer, Ruifang Li-Gao, Dina Vojinovic, Najaf Amin, Djawad Radjabzadeh, Robert Kraaij, Louise J.M. Alferink, Sarwa Darwish MuradAndré G. Uitterlinden, Gonneke Willemsen, Rene Pool, Yuri Milaneschi, Diana van Heemst, H. Eka D. Suchiman, Femke Rutters, Petra J.M. Elders, Joline W.J. Beulens, Amber A.W.A. van der Heijden, Marleen M.J. van Greevenbroek, Ilja C.W. Arts, Gerrit L.J. Onderwater, Arn M.J.M. van den Maagdenberg, Dennis O. Mook-Kanamori, Thomas Hankemeier, Gisela M. Terwindt, Coen D.A. Stehouwer, Johanna M. Geleijnse, Leen M. ‘t Hart, P. Eline Slagboom, Ko Willems van Dijk, Alexandra Zhernakova, Jingyuan Fu, Brenda W.J.H. Penninx, Dorret I. Boomsma, Ayşe Demirkan, Bruno H.C. Stricker, Cornelia M. van Duijn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)110-117
Number of pages8
JournalNature Medicine
Volume26
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

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