Cross-Platform Calibration of Epigenetic Age Between the EPICv2 and MSA Arrays

Epigenetic clocks are regression models that predict biological age based on the DNA methylation patterns. They are developed using DNA methylation array data; however, systematic differences in the predicted values between the Infinium Methylation Screening Array (MSA) and Infinium MethylationEPIC v2.0 BeadChip (EPICv2) platforms have not been evaluated. We quantified the systematic differences between the MSA and EPICv2 arrays for six major epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, GrimAge v2, and DunedinPACE) using 166 identical human blood samples measured on both platforms. The mean differences (MSA - EPICv2) ranged from -7.99 years for PhenoAge to 21.8 years for the Hannum clock, despite strong correlations between platforms (r = 0.854 - 0.991). Based on these training data, we developed three linear regression models to correct the MSA-based epigenetic clocks: Model 1 (offset location correction), Model 2 (slope and location correction), and Model 3 (slope and location correction with covariates). Validation on 48 independent samples measured at a different institution showed that all models reduced cross-platform bias. Although Model 3 tended to achieve the lowest bias; 0.204 years for PhenoAge and 0.383 years for GrimAge v2, Model 1, which was the simplest, provided a sufficient correction: -0.541 years of bias for PhenoAge and 0.516 for GrimAge v2. These methods are expected to enable reliable comparisons of epigenetic age across platforms and facilitate large-scale epigenetic studies.