@article{726bdcdb95544efb898d6cd5b333052d,
title = "NMR metabolomics-guided DNA methylation mortality predictors",
abstract = "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.",
keywords = "Ageing biomarkers, DNA methylation predictors, Epidemiology, Epigenetic clock, Metabolic risk score, NMR metabolomics",
author = "{BBMRI Consortium} and Daniele Bizzarri and Reinders, {Marcel J.T.} and Lieke Kuiper and Marian Beekman and Joris Deelen and {van Meurs}, {Joyce B.J.} and {van Dongen}, Jenny and Ren{\'e} Pool and Boomsma, {Dorret I.} and M. Ghanbari and Lude Franke and Geleijnse, {J. M.} and E. Boersma and {van Spil}, {W. E.} and {van Greevenbroek}, {M. M.J.} and Stehouwer, {C. D.A.} and {van der Kallen}, {C. J.H.} and Arts, {I. C.W.} and F. Rutters and Beulens, {J. W.J.} and M. Muilwijk and Elders, {P. J.M.} and {'t Hart}, {L. M.} and M. Ghanbari and Ikram, {M. A.} and Netea, {M. G.} and M. Kloppenburg and Ramos, {Y. F.M.} and N. Bomer and Snijder, {M. B.} and C. Wijmenga and J. Fu and A. Zhernakova and J. Deelen and M. Beekman and Onderwater, {G. L.J.} and Penninx, {B. W.J.H.} and Jukema, {J. W.} and {van der Horst}, {I. C.C.} and {van der Harst}, P. and Asselbergs, {F. W.} and Teunissen, {C. E.} and {van Dongen}, J. and R. Pool and Willemsen, {A. H.M.} and Boomsma, {D. I.} and H. Mei and M. Slofstra and M. Swertz and Reinders, {M. J.T.}",
note = "Publisher Copyright: {\textcopyright} 2024 The Authors",
year = "2024",
month = sep,
doi = "10.1016/j.ebiom.2024.105279",
language = "English",
volume = "107",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "ELSEVIER SCIENCE BV",
}