Cited 4 times since 2024 (4 per year) source: EuropePMC EBioMedicine, Volume 107, 17 3 2024, Pages 105279 NMR metabolomics-guided DNA methylation mortality predictors. Bizzarri D, Reinders MJT, Kuiper L, Beekman M, Deelen J, van Meurs JBJ, van Dongen J, Pool R, Boomsma DI, Ghanbari M, Franke L, BBMRI Consortium, Slagboom PE, van den Akker EB
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.
