DNAm age differences between infinium methylationEPICv1 vs EPICv2 in buffy coat, PBMC, and saliva samples

This study aims to evaluate differences between Infinium MethylationEPIC (EPICv1) and Infinium MethylationEPICv2 (EPICv2) arrays in estimating DNAm age with eleven DNAm clocks using buffy coat, peripheral blood mononuclear cell (PBMC), and saliva from 16 healthy middle-aged individuals. DNAm ages were estimated using six principal component-based (PC) clocks (PCHorvath1, PCHorvath2, PCHannum, PCPhenoAge, PCGrimAge, and PCDNAmTL) and five non-PC clocks (DunedinPACE, DNAmFit, YingCausAge, YingAdaptAge, and YingDamAge) across all biological samples. Agreement between arrays was assessed using Spearman correlation, Bland-Altman plots, and Wilcoxon Signed-Rank test. The 16 individuals with median age of 48 43.5;53.8 years, were predominantly female, Chinese and non-smokers. High correlations (ρ > 0.8) were observed between EPICv1 and EPICv2 except for DunedinPACE, YingDamAge and YingAdaptAge. PC-based clocks showed lower systematic bias (MAPE:0.118-8.98%) compared to non-PC-based clocks (MAPE:5.31-21.2%). Saliva samples demonstrated greatest variability between arrays. EPICv2 introduces systematic biases especially in non-PC-based clocks and between different biological samples.