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 Murad, André 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

Journal: Nature medicine 2020;26(1):110-117

PMID: 31932804

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/).

Address: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. [email protected].; Nuffield Department of Population Health, University of Oxford, Oxford, UK. [email protected].; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.; Department of Biological Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.; Department of Genetics, University Medical Center Groningen, Groningen, the Netherlands.; Department of Pediatrics, University Medical Center Groningen, Groningen, the Netherlands.; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.; Department of Clinical Chemistry, Laboratory Genetic Metabolic Disease, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Department of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Pattern Recognition and Bioinformatics, Delft University of Technology, Delft, the Netherlands.; Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.; Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.; Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands.; Department of Internal Medicine, Maastricht University, Maastricht, the Netherlands.; School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.; Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.; Department of General Practice and Elderly Care Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.; School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.; Department of Epidemiology, Maastricht University, Maastricht, the Netherlands.; Maastricht Center for Systems Biology, Maastricht University, Maastricht, the Netherlands.; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.; Leiden Academic Center for Drug Research, Leiden University, Leiden, the Netherlands.; Netherlands Metabolomics Center, Leiden, the Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.; Department of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.; Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Genetics, University Medical Center Groningen, Groningen, the Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Department of Genetics, University Medical Center Groningen, Groningen, the Netherlands.; Section of Statistical Multi-omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.; Inspectorate of Healthcare, The Hague, the Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. [email protected].; Nuffield Department of Population Health, University of Oxford, Oxford, UK. [email protected].; Leiden Academic Center for Drug Research, Leiden University, Leiden, the Netherlands. [email protected].

Link outs

Subscription / membership required

Bant logo

© Copyright 2026, Nutrition Evidence

NED wishes to thank the following organisations for their support:

We use cookies to improve your experience and analyze site traffic with Google Analytics. By continuing to use our site, you agree to our use of cookies. Learn more.