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

doi:10.1038/s41591-019-0722-x

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

Journal article

Peer reviewed

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, …

Nature medicine, Vol.26(1), pp.110-117

01/01/2020

DOI: https://doi.org/10.1038/s41591-019-0722-x

PMID: 31932804

Abstract

Body Mass Index

Confounding Factors, Epidemiologic

Endophenotypes

Epidemiologic Studies

Gastrointestinal Microbiome - genetics

Humans

Liver - metabolism

Metabolome - genetics

Models, Biological

Pharmaceutical Preparations

Protein Interaction Maps

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/).

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Title: Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas
Creators: Jun Liu - Erasmus MC
Lies Lahousse - Erasmus MC
Michel G Nivard - Vrije Universiteit Amsterdam
Mariska Bot - Vrije Universiteit Amsterdam
Lianmin Chen - University Medical Center Groningen
Jan Bert van Klinken - Leiden University Medical Center
Carisha S Thesing - Vrije Universiteit Amsterdam
Marian Beekman - Leiden University Medical Center
Erik Ben van den Akker - Leiden University Medical Center
Roderick C Slieker - Vrije Universiteit Amsterdam
Eveline Waterham - Wageningen University & Research
Carla J H van der Kallen - Maastricht University
Irene de Boer - Leiden University Medical Center
Ruifang Li-Gao - Leiden University Medical Center
Dina Vojinovic - Erasmus MC
Najaf Amin - Erasmus MC
Djawad Radjabzadeh - Erasmus MC
Robert Kraaij - Erasmus MC
Louise J M Alferink - Erasmus MC
Sarwa Darwish Murad - Erasmus MC
André G Uitterlinden - Erasmus MC
Gonneke Willemsen - Vrije Universiteit Amsterdam
Rene Pool - Vrije Universiteit Amsterdam
Yuri Milaneschi - Vrije Universiteit Amsterdam
Diana van Heemst - Leiden University Medical Center
H Eka D Suchiman - Leiden University Medical Center
Femke Rutters - Vrije Universiteit Amsterdam
Petra J M Elders - Department of General Practice and Elderly Care Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands
Joline W J Beulens - Vrije Universiteit Amsterdam
Amber A W A van der Heijden - Vrije Universiteit Amsterdam
Marleen M J van Greevenbroek - Maastricht University
Ilja C W Arts - Maastricht University
Gerrit L J Onderwater - Leiden University Medical Center
Arn M J M van den Maagdenberg - Leiden University Medical Center
Dennis O Mook-Kanamori - Leiden University Medical Center
Thomas Hankemeier - Netherlands Metabolomics Centre
Gisela M Terwindt - Leiden University Medical Center
Coen D A Stehouwer - Maastricht University
Johanna M Geleijnse - Wageningen University & Research
Leen M 't Hart - Leiden University Medical Center
P Eline Slagboom - Leiden University Medical Center
Ko Willems van Dijk - Leiden University Medical Center
Alexandra Zhernakova - University Medical Center Groningen
Jingyuan Fu - University Medical Center Groningen
Brenda W J H Penninx - Vrije Universiteit Amsterdam
Dorret I Boomsma - Vrije Universiteit Amsterdam
Ayşe Demirkan - University of Surrey
Bruno H C Stricker - Erasmus MC
Cornelia M van Duijn - Erasmus MC
Publication Details: Nature medicine, Vol.26(1), pp.110-117
Date published: 01/01/2020
Identifiers: 99828461602346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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