Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas.
Jun LiuLies LahousseMichel G NivardMariska BotLianmin ChenJan Bert van KlinkenCarisha S ThesingMarian BeekmanErik Ben van den AkkerRoderick C SliekerEveline WaterhamCarla J H van der KallenIrene de BoerRuifang Li-GaoDina VojinovicNajaf AminDjawad RadjabzadehRobert KraaijLouise J M AlferinkSarwa Darwish MuradAndre G UitterlindenGonneke WillemsenRené PoolYuri MilaneschiDiana van HeemstEka H E D SuchimanFemke RuttersPetra J M EldersJoline W J BeulensAmber A W A van der HeijdenMarleen M J van GreevenbroekIlja C W ArtsGerrit L J OnderwaterArn M J M van den MaagdenbergDennis O Mook-KanamoriThomas HankemeierGisela M TerwindtCoen D A StehouwerJohanna Marianna GeleijnseLeen M 't HartPieternella Eline SlagboomKo Willems van DijkAlexandra ZhernakovaJingyuan FuBrenda W J H PenninxDorret I BoomsmaAyşe DemirkanBruno H C StrickerCornelia M Van DuijnPublished in: Nature medicine (2020)
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/).