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Article Abstract
Background: H-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 H-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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378104 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2024.105279 | DOI Listing |
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