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

J. Liu; L. Lahousse; M.G. Nivard; M. Bot; L.M. Chen; J.B. van Klinken; C.S. Thesing; M. Beekman; E.B. van den Akker; R.C. Slieker; E. Waterham; C.J.H. van der Kallen; I. de Boer; R.F. Li-Gao; D. Vojinovic; N. Amin; D. Radjabzadeh; R. Kraaij; L.J.M. Alferink; S.D. Murad; A.G. Uitterlinden; G. Willemsen; R. Pool; Y. Milaneschi; D. van Heemst; H.E.D. Suchiman; F. Rutters; P.J.M. Elders; J.W.J. Beulens; A.A.W.A. van der Heijden; M.M.J. van Greevenbroek; I.C.W. Arts; G.L.J. Onderwater; A.M.J.M. van den Maagdenberg; D.O. Mook-Kanamori; T. Hankemeier; G.M. Terwindt; C.D.A. Stehouwer; J.M. Geleijnse; L.M. 't Hart; P.E. Slagboom; K.W. van Dijk; A. Zhernakova; J.Y. Fu; B.W.J.H. Penninx; D.I. Boomsma; A. Demirkan; B.H.C. Stricker; C.M. van Duijn

doi:10.1038/s41591-019-0722-x

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

J. Liu^*, L. Lahousse, M.G. Nivard, M. Bot, L.M. Chen, J.B. van Klinken, C.S. Thesing, M. Beekman, E.B. van den Akker, R.C. Slieker, E. Waterham, C.J.H. van der Kallen, I. de Boer, R.F. Li-Gao, D. Vojinovic, N. Amin, D. Radjabzadeh, R. Kraaij, L.J.M. Alferink, S.D. MuradA.G. Uitterlinden, G. Willemsen, R. Pool, Y. Milaneschi, D. van Heemst, H.E.D. Suchiman, F. Rutters, P.J.M. Elders, J.W.J. Beulens, A.A.W.A. van der Heijden, M.M.J. van Greevenbroek, I.C.W. Arts, G.L.J. Onderwater, A.M.J.M. van den Maagdenberg, D.O. Mook-Kanamori, T. Hankemeier, G.M. Terwindt, C.D.A. Stehouwer, J.M. Geleijnse, L.M. 't Hart, P.E. Slagboom, K.W. van Dijk, A. Zhernakova, J.Y. Fu, B.W.J.H. Penninx, D.I. Boomsma, A. Demirkan, B.H.C. Stricker, C.M. van Duijn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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/).

Original language	English
Pages (from-to)	110-117
Number of pages	20
Journal	Nature Medicine
Volume	26
Issue number	1
DOIs	https://doi.org/10.1038/s41591-019-0722-x
Publication status	Published - 1 Jan 2020

Keywords

circulating metabolites
design
diabetes-mellitus
magnetic-resonance metabolomics
mendelian randomization
obesity
population
profiles
risk
serum metabolome
POPULATION
PROFILES
DESIGN
SERUM METABOLOME
RISK
MENDELIAN RANDOMIZATION
CIRCULATING METABOLITES
DIABETES-MELLITUS
MAGNETIC-RESONANCE METABOLOMICS
OBESITY

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10.1038/s41591-019-0722-x

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Cite this

Liu, J., Lahousse, L., Nivard, M. G., Bot, M., Chen, L. M., van Klinken, J. B., Thesing, C. S., Beekman, M., van den Akker, E. B., Slieker, R. C., Waterham, E., van der Kallen, C. J. H., de Boer, I., Li-Gao, R. F., Vojinovic, D., Amin, N., Radjabzadeh, D., Kraaij, R., Alferink, L. J. M., ... van Duijn, C. M. (2020). Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas. Nature Medicine, 26(1), 110-117. https://doi.org/10.1038/s41591-019-0722-x

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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/).",

keywords = "circulating metabolites, design, diabetes-mellitus, magnetic-resonance metabolomics, mendelian randomization, obesity, population, profiles, risk, serum metabolome, POPULATION, PROFILES, DESIGN, SERUM METABOLOME, RISK, MENDELIAN RANDOMIZATION, CIRCULATING METABOLITES, DIABETES-MELLITUS, MAGNETIC-RESONANCE METABOLOMICS, OBESITY",

author = "J. Liu and L. Lahousse and M.G. Nivard and M. Bot and L.M. Chen and {van Klinken}, J.B. and C.S. Thesing and M. Beekman and {van den Akker}, E.B. and R.C. Slieker and E. Waterham and {van der Kallen}, C.J.H. and {de Boer}, I. and R.F. Li-Gao and D. Vojinovic and N. Amin and D. Radjabzadeh and R. Kraaij and L.J.M. Alferink and S.D. Murad and A.G. Uitterlinden and G. Willemsen and R. Pool and Y. Milaneschi and {van Heemst}, D. and H.E.D. Suchiman and F. Rutters and P.J.M. Elders and J.W.J. Beulens and {van der Heijden}, A.A.W.A. and {van Greevenbroek}, M.M.J. and I.C.W. Arts and G.L.J. Onderwater and {van den Maagdenberg}, A.M.J.M. and D.O. Mook-Kanamori and T. Hankemeier and G.M. Terwindt and C.D.A. Stehouwer and J.M. Geleijnse and {'t Hart}, L.M. and P.E. Slagboom and {van Dijk}, K.W. and A. Zhernakova and J.Y. Fu and B.W.J.H. Penninx and D.I. Boomsma and A. Demirkan and B.H.C. Stricker and {van Duijn}, C.M.",

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doi = "10.1038/s41591-019-0722-x",

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Liu, J, Lahousse, L, Nivard, MG, Bot, M, Chen, LM, van Klinken, JB, Thesing, CS, Beekman, M, van den Akker, EB, Slieker, RC, Waterham, E, van der Kallen, CJH, de Boer, I, Li-Gao, RF, Vojinovic, D, Amin, N, Radjabzadeh, D, Kraaij, R, Alferink, LJM, Murad, SD, Uitterlinden, AG, Willemsen, G, Pool, R, Milaneschi, Y, van Heemst, D, Suchiman, HED, Rutters, F, Elders, PJM, Beulens, JWJ, van der Heijden, AAWA, van Greevenbroek, MMJ , Arts, ICW, Onderwater, GLJ, van den Maagdenberg, AMJM, Mook-Kanamori, DO, Hankemeier, T, Terwindt, GM, Stehouwer, CDA, Geleijnse, JM, 't Hart, LM, Slagboom, PE, van Dijk, KW, Zhernakova, A, Fu, JY, Penninx, BWJH, Boomsma, DI, Demirkan, A, Stricker, BHC & van Duijn, CM 2020, 'Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas', Nature Medicine, vol. 26, no. 1, pp. 110-117. https://doi.org/10.1038/s41591-019-0722-x

TY - JOUR

T1 - Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas

AU - Liu, J.

AU - Lahousse, L.

AU - Nivard, M.G.

AU - Bot, M.

AU - Chen, L.M.

AU - van Klinken, J.B.

AU - Thesing, C.S.

AU - Beekman, M.

AU - van den Akker, E.B.

AU - Slieker, R.C.

AU - Waterham, E.

AU - van der Kallen, C.J.H.

AU - de Boer, I.

AU - Li-Gao, R.F.

AU - Vojinovic, D.

AU - Amin, N.

AU - Radjabzadeh, D.

AU - Kraaij, R.

AU - Alferink, L.J.M.

AU - Murad, S.D.

AU - Uitterlinden, A.G.

AU - Willemsen, G.

AU - Pool, R.

AU - Milaneschi, Y.

AU - van Heemst, D.

AU - Suchiman, H.E.D.

AU - Rutters, F.

AU - Elders, P.J.M.

AU - Beulens, J.W.J.

AU - van der Heijden, A.A.W.A.

AU - van Greevenbroek, M.M.J.

AU - Arts, I.C.W.

AU - Onderwater, G.L.J.

AU - van den Maagdenberg, A.M.J.M.

AU - Mook-Kanamori, D.O.

AU - Hankemeier, T.

AU - Terwindt, G.M.

AU - Stehouwer, C.D.A.

AU - Geleijnse, J.M.

AU - 't Hart, L.M.

AU - Slagboom, P.E.

AU - van Dijk, K.W.

AU - Zhernakova, A.

AU - Fu, J.Y.

AU - Penninx, B.W.J.H.

AU - Boomsma, D.I.

AU - Demirkan, A.

AU - Stricker, B.H.C.

AU - van Duijn, C.M.

PY - 2020/1/1

Y1 - 2020/1/1

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/).

KW - circulating metabolites

KW - design

KW - diabetes-mellitus

KW - magnetic-resonance metabolomics

KW - mendelian randomization

KW - obesity

KW - population

KW - profiles

KW - risk

KW - serum metabolome

KW - POPULATION

KW - PROFILES

KW - DESIGN

KW - SERUM METABOLOME

KW - RISK

KW - MENDELIAN RANDOMIZATION

KW - CIRCULATING METABOLITES

KW - DIABETES-MELLITUS

KW - MAGNETIC-RESONANCE METABOLOMICS

KW - OBESITY

U2 - 10.1038/s41591-019-0722-x

DO - 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 -