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Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas.
Liu, Jun; Lahousse, Lies; Nivard, Michel G; Bot, Mariska; Chen, Lianmin; van Klinken, Jan Bert; Thesing, Carisha S; Beekman, Marian; van den Akker, Erik Ben; Slieker, Roderick C; Waterham, Eveline; van der Kallen, Carla J H; de Boer, Irene; Li-Gao, Ruifang; Vojinovic, Dina; Amin, Najaf; Radjabzadeh, Djawad; Kraaij, Robert; Alferink, Louise J M; Murad, Sarwa Darwish; Uitterlinden, André G; Willemsen, Gonneke; Pool, Rene; Milaneschi, Yuri; van Heemst, Diana; Suchiman, H Eka D; Rutters, Femke; Elders, Petra J M; Beulens, Joline W J; van der Heijden, Amber A W A; van Greevenbroek, Marleen M J; Arts, Ilja C W; Onderwater, Gerrit L J; van den Maagdenberg, Arn M J M; Mook-Kanamori, Dennis O; Hankemeier, Thomas; Terwindt, Gisela M; Stehouwer, Coen D A; Geleijnse, Johanna M; 't Hart, Leen M; Slagboom, P Eline; van Dijk, Ko Willems; Zhernakova, Alexandra; Fu, Jingyuan; Penninx, Brenda W J H; Boomsma, Dorret I; Demirkan, Ayse; Stricker, Bruno H C; van Duijn, Cornelia M.
Afiliación
  • Liu J; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. jun.liu@ndph.ox.ac.uk.
  • Lahousse L; Nuffield Department of Population Health, University of Oxford, Oxford, UK. jun.liu@ndph.ox.ac.uk.
  • Nivard MG; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Bot M; Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
  • Chen L; Department of Biological Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • van Klinken JB; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Thesing CS; Department of Biological Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • Beekman M; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • van den Akker EB; Department of Genetics, University Medical Center Groningen, Groningen, the Netherlands.
  • Slieker RC; Department of Pediatrics, University Medical Center Groningen, Groningen, the Netherlands.
  • Waterham E; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • van der Kallen CJH; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
  • de Boer I; Department of Clinical Chemistry, Laboratory Genetic Metabolic Disease, Amsterdam University Medical Center, Amsterdam, the Netherlands.
  • Li-Gao R; Department of Biological Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • Vojinovic D; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Amin N; Department of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
  • Radjabzadeh D; Department of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
  • Kraaij R; Department of Pattern Recognition and Bioinformatics, Delft University of Technology, Delft, the Netherlands.
  • Alferink LJM; Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands.
  • Murad SD; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Uitterlinden AG; Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • Willemsen G; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
  • Pool R; Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands.
  • Milaneschi Y; Department of Internal Medicine, Maastricht University, Maastricht, the Netherlands.
  • van Heemst D; School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
  • Suchiman HED; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
  • Rutters F; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
  • Elders PJM; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Beulens JWJ; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • van der Heijden AAWA; Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • van Greevenbroek MMJ; Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Arts ICW; Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Onderwater GLJ; Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • van den Maagdenberg AMJM; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Mook-Kanamori DO; Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Hankemeier T; Department of Biological Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • Terwindt GM; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Stehouwer CDA; Department of Biological Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • Geleijnse JM; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • 't Hart LM; Department of Biological Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • Slagboom PE; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • van Dijk KW; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
  • Zhernakova A; Department of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
  • Fu J; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Penninx BWJH; Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • Boomsma DI; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Demirkan A; Department of General Practice and Elderly Care Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
  • Stricker BHC; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • van Duijn CM; Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Nat Med ; 26(1): 110-117, 2020 01.
Article en En | MEDLINE | ID: mdl-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/).
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas / Estudios Epidemiológicos / Metaboloma / Microbioma Gastrointestinal Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Países Bajos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas / Estudios Epidemiológicos / Metaboloma / Microbioma Gastrointestinal Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Países Bajos