EBioMedicine (Sep 2024)
NMR metabolomics-guided DNA methylation mortality predictorsResearch in context
- Daniele Bizzarri,
- Marcel J.T. Reinders,
- Lieke Kuiper,
- Marian Beekman,
- Joris Deelen,
- Joyce B.J. van Meurs,
- Jenny van Dongen,
- René Pool,
- Dorret I. Boomsma,
- Mohsen Ghanbari,
- Lude Franke,
- Pieternella E. Slagboom,
- Erik B. van den Akker,
- J.M. Geleijnse,
- E. Boersma,
- W.E. van Spil,
- M.M.J. van Greevenbroek,
- C.D.A. Stehouwer,
- C.J.H. van der Kallen,
- I.C.W. Arts,
- F. Rutters,
- J.W.J. Beulens,
- M. Muilwijk,
- P.J.M. Elders,
- L.M. 't Hart,
- M. Ghanbari,
- M.A. Ikram,
- M.G. Netea,
- M. Kloppenburg,
- Y.F.M. Ramos,
- N. Bomer,
- I. Meulenbelt,
- K. Stronks,
- M.B. Snijder,
- A.H. Zwinderman,
- B.T. Heijmans,
- L.H. Lumey,
- C. Wijmenga,
- J. Fu,
- A. Zhernakova,
- J. Deelen,
- S.P. Mooijaart,
- M. Beekman,
- P.E. Slagboom,
- G.L.J. Onderwater,
- A.M.J.M. van den Maagdenberg,
- G.M. Terwindt,
- C. Thesing,
- M. Bot,
- B.W.J.H. Penninx,
- S. Trompet,
- J.W. Jukema,
- N. Sattar,
- I.C.C. van der Horst,
- P. van der Harst,
- C. So-Osman,
- J.A. van Hilten,
- R.G.H.H. Nelissen,
- I.E. Höfer,
- F.W. Asselbergs,
- P. Scheltens,
- C.E. Teunissen,
- W.M. van der Flier,
- J. van Dongen,
- R. Pool,
- A.H.M. Willemsen,
- D.I. Boomsma,
- H.E.D. Suchiman,
- J.J.H. Barkey Wolf,
- M. Beekman,
- D. Cats,
- H. Mei,
- M. Slofstra,
- M. Swertz,
- M.J.T. Reinders,
- E.B. van den Akker,
- D.I. Boomsma,
- M.A. Ikram,
- P.E. Slagboom
Affiliations
- Daniele Bizzarri
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Leiden Computational Biology Center, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Delft Bioinformatics Lab, TU Delft, Delft, the Netherlands
- Marcel J.T. Reinders
- Leiden Computational Biology Center, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Delft Bioinformatics Lab, TU Delft, Delft, the Netherlands
- Lieke Kuiper
- Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Center for Nutrition, Prevention and Health Services, National Institute for Public Health and Environment (RIVM), Bilthoven, the Netherlands
- Marian Beekman
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands
- Joris Deelen
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Max Planck Institute for the Biology of Ageing, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne, Germany
- Joyce B.J. van Meurs
- Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands; Department of Orthopaedics & Sports, Erasmus Medical Center, Rotterdam, the Netherlands
- Jenny van Dongen
- Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
- René Pool
- Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
- Dorret I. Boomsma
- Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
- Mohsen Ghanbari
- Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands
- Lude Franke
- Department of Genetics, University Medical Center Groningen, Groningen, the Netherlands
- Pieternella E. Slagboom
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Max Planck Institute for the Biology of Ageing, Cologne, Germany
- Erik B. van den Akker
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Leiden Computational Biology Center, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Delft Bioinformatics Lab, TU Delft, Delft, the Netherlands; Corresponding author. Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2333, ZC, Leiden, the Netherlands.
- J.M. Geleijnse
- E. Boersma
- W.E. van Spil
- M.M.J. van Greevenbroek
- C.D.A. Stehouwer
- C.J.H. van der Kallen
- I.C.W. Arts
- F. Rutters
- J.W.J. Beulens
- M. Muilwijk
- P.J.M. Elders
- L.M. 't Hart
- M. Ghanbari
- M.A. Ikram
- M.G. Netea
- M. Kloppenburg
- Y.F.M. Ramos
- N. Bomer
- I. Meulenbelt
- K. Stronks
- M.B. Snijder
- A.H. Zwinderman
- B.T. Heijmans
- L.H. Lumey
- C. Wijmenga
- J. Fu
- A. Zhernakova
- J. Deelen
- S.P. Mooijaart
- M. Beekman
- P.E. Slagboom
- G.L.J. Onderwater
- A.M.J.M. van den Maagdenberg
- G.M. Terwindt
- C. Thesing
- M. Bot
- B.W.J.H. Penninx
- S. Trompet
- J.W. Jukema
- N. Sattar
- I.C.C. van der Horst
- P. van der Harst
- C. So-Osman
- J.A. van Hilten
- R.G.H.H. Nelissen
- I.E. Höfer
- F.W. Asselbergs
- P. Scheltens
- C.E. Teunissen
- W.M. van der Flier
- J. van Dongen
- R. Pool
- A.H.M. Willemsen
- D.I. Boomsma
- H.E.D. Suchiman
- J.J.H. Barkey Wolf
- M. Beekman
- D. Cats
- H. Mei
- M. Slofstra
- M. Swertz
- M.J.T. Reinders
- E.B. van den Akker
- D.I. Boomsma
- M.A. Ikram
- P.E. Slagboom
- Journal volume & issue
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Vol. 107
p. 105279
Abstract
Summary: Background: 1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals. Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors. Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates. Interpretation: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal. Funding: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC.
