NMR metabolomics-guided DNA methylation mortality predictors.
EBioMedicine
; 107: 105279, 2024 Aug 17.
Article
em En
| MEDLINE
| ID: mdl-39154540
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, â¼40% 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.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article