TY - JOUR
T1 - Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas
AU - Liu, Jun
AU - Lahousse, Lies
AU - Nivard, Michel G
AU - Bot, Mariska
AU - Chen, Lianmin
AU - van Klinken, Jan Bert
AU - Thesing, Carisha S
AU - Beekman, Marian
AU - van den Akker, Erik Ben
AU - Slieker, Roderick C
AU - Waterham, Eveline
AU - van der Kallen, Carla J H
AU - de Boer, Irene
AU - Li-Gao, Ruifang
AU - Vojinovic, Dina
AU - Amin, Najaf
AU - Radjabzadeh, Djawad
AU - Kraaij, Robert
AU - Alferink, Louise J M
AU - Murad, Sarwa Darwish
AU - Uitterlinden, André G
AU - Willemsen, Gonneke
AU - Pool, Rene
AU - Milaneschi, Yuri
AU - van Heemst, Diana
AU - Suchiman, H Eka D
AU - Rutters, Femke
AU - Elders, Petra J M
AU - Beulens, Joline W J
AU - van der Heijden, Amber A W A
AU - van Greevenbroek, Marleen M J
AU - Arts, Ilja C W
AU - Onderwater, Gerrit L J
AU - van den Maagdenberg, Arn M J M
AU - Mook-Kanamori, Dennis O
AU - Hankemeier, Thomas
AU - Terwindt, Gisela M
AU - Stehouwer, Coen D A
AU - Geleijnse, Johanna M
AU - 't Hart, Leen M
AU - Slagboom, P Eline
AU - van Dijk, Ko Willems
AU - Zhernakova, Alexandra
AU - Fu, Jingyuan
AU - Penninx, Brenda W J H
AU - Boomsma, Dorret I
AU - Demirkan, Ayşe
AU - Stricker, Bruno H C
AU - van Duijn, Cornelia M
PY - 2020/1
Y1 - 2020/1
N2 - 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/).
AB - 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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U2 - https://doi.org/10.1038/s41591-019-0722-x
DO - https://doi.org/10.1038/s41591-019-0722-x
M3 - Article
C2 - 31932804
SN - 1078-8956
VL - 26
SP - 110
EP - 117
JO - Nature Medicine
JF - Nature Medicine
IS - 1
ER -