Summary
Chronological age prediction from DNA methylation sheds light on human aging, indicates poor health and predicts lifespan. Current clocks are mostly based on linear models from hundreds of methylation sites, and are not suitable for sequencing-based data.
We present GP-age, an epigenetic clock for blood, that uses a non-linear cohort-based model of 11,910 blood methylomes. Using 30 CpG sites alone, GP-age outperforms state-of-the-art models, with a median accuracy of ~2 years on held-out blood samples, for both array and sequencing-based data. We show that aging-related changes occur at multiple neighboring CpGs, with far-reaching implications on aging research at the cellular level. By training three independent clocks, we show consistent deviations between predicted and actual age, suggesting individual rates of biological aging.
Overall, we provide a compact yet accurate alternative to array-based clocks for blood, with future applications in longitudinal aging research, forensic profiling, and monitoring epigenetic processes in transplantation medicine and cancer.
Machine learning analysis of a large cohort (~12K) of DNA methylomes from blood
A 30-CpG regression model achieves a 2.1-year median error in predicting age
Improved accuracy (≥1.75 years) from sequencing data, using neighboring CpGs
Paves the way for easy and accurate age prediction from blood, using NGS data
Motivation Epigenetic clocks that predict age from DNA methylation are a valuable tool in the research of human aging, with additional applications in forensic profiling, disease monitoring, and lifespan prediction. Most existing epigenetic clocks are based on linear models and require hundreds of methylation sites. Here, we present a compact epigenetic clock for blood, which outperforms state-of-the-art models using only 30 CpG sites. Finally, we demonstrate the applicability of our clock to sequencing-based data, with far reaching implications for a better understanding of epigenetic aging.
Competing Interest Statement
The authors have declared no competing interest.