12: From Mean to Quantiles: Post-hoc Quantile Calibration of Epigenetic Age Clocks

Thomas M. Menino Convention & Exhibition Center 

Quantiles of epigenetic age provide clinically meaningful information about heterogeneity in aging trajectories, enabling identification of individuals who age faster or slower than their peers beyond mean-based assessments. However, widely used epigenetic clocks primarily output mean predictions and do not directly provide quantile estimates or calibrated uncertainty. We propose a residual-based model switching framework that converts an existing mean epigenetic clock into a quantile clock without refitting the underlying methylation-to-age model. The method estimates global or conditional residual quantiles and yields calibrated quantile predictions of epigenetic age under mild assumptions. We provide theoretical justification, practical algorithms, and open-source software, and demonstrate the approach through simulations and applications to two real-world datasets across commonly used epigenetic clocks.

Biological age

Epigenetic age clocks

Quantile calibration

Conformal prediction

Prediction intervals 

Biometrics Section