ArticlemedRxiv : the preprint server for health sciences2025
An unbiased comparison of 14 epigenetic clocks in relation to 10-year onset of 174 disease outcomes in 18,859 individuals.
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Epigenetic Clocks have been trained to predict chronological age, healthspan and lifespan. Such clocks are often analysed in relation to disease outcomes - typically using small datasets and a limited number of clocks. Here, we present the first large-scale (n=18,849), unbiased comparison of 14 widely used clocks as predictors of 174 incident disease outcomes and all-cause mortality. Second-generation clocks significantly outperformed first-generation clocks, which have limited applications in disease settings. Of the 176 Bonferroni significant (P<0.05/174) associations, there were 27 diseases (including primary lung cancer and diabetes) where the hazard ratio for the clock exceeded the clock's association with all-cause mortality. Furthermore, there were 35 instances where adding a clock to a null classification model with traditional risk factors increased the classification accuracy by >1% with an AUC
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