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.
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
Overview publication
| Title | NMR metabolomics-guided DNA methylation mortality predictors. |
| Date | August 17th, 2024 |
| Issue name | EBioMedicine |
| Issue number | v107:105279 |
| DOI | 10.1016/j.ebiom.2024.105279 |
| PubMed | 39154540 |
| Authors | |
| Info | BBMRI Consortium, Geleijnse JM, Boersma E, van Spil WE, van Greevenbroek MMJ, Stehouwer CDA, van der Kallen CJH, Arts ICW, Rutters F, Beulens JWJ, Muilwijk M, Elders PJM, 't Hart LM, Ghanbari M, Ikram MA, Netea MG, Kloppenburg M, Ramos YFM, Bomer N, Meulenbelt I, Stronks K, Snijder MB, Zwinderman AH, Heijmans BT, Lumey LH, Wijmenga C, Fu J, Zhernakova A, Deelen J, Mooijaart SP, Beekman M, Slagboom PE, Onderwater GLJ, van den Maagdenberg AMJM, Terwindt GM, Thesing C, Bot M, Penninx BWJH, Trompet S, Jukema JW, Sattar N, van der Horst ICC, van der Harst P, So-Osman C, van Hilten JA, Nelissen RGHH, Höfer IE, Asselbergs FW, Scheltens P, Teunissen CE, van der Flier WM, van Dongen J, Pool R, Willemsen AHM, Boomsma DI, Suchiman HED, Barkey Wolf JJH, Beekman M, Cats D, Mei H, Slofstra M, Swertz M, Reinders MJT, van den Akker EB, Boomsma DI, Ikram MA, Slagboom PE |
| Keywords | Ageing biomarkers, DNA methylation predictors, Epidemiology, Epigenetic clock, Metabolic risk score, NMR metabolomics |
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