DNA methylation marker identification and poly-methylation risk score in prediction of healthspan termination
Abstract
Aim: To elucidate the epigenetic consequences of DNA methylation in healthspan termination (HST), considering the current limited understanding. Materials & methods: Genetically predicted DNA methylation models were established (n = 2478). These models were applied to genome-wide association study data on HST. Then, a poly-methylation risk score (PMRS) was established in 241,008 individuals from the UK Biobank. Results: Of the 63,046 CpGs from the prediction models, 13 novel CpGs were associated with HST. Furthermore, people with high PMRSs showed higher HST risk (hazard ratio: 1.18; 95% CI: 1.13–1.25). Conclusion: The study indicates that DNA methylation may influence HST by regulating the expression of genes (e.g., PRMT6, CTSK). PMRSs have a promising application in discriminating subpopulations to facilitate early prevention.
Tweetable abstract
The concept of the ‘healthspan’, the time an individual remains morbidity-free, requires more attention. Poly-methylation risk scores have a promising application in discriminating subpopulations at risk of healthspan termination to facilitate early prevention.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
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