Probing buccal-customized epigenetic clocks to investigate socioeconomic and health disparities.

Epigenetic clocks are emerging as promising tools for examining social and health disparities. These measures are typically developed using blood DNA methylation (DNAm) data. Cheek swabs, being less invasive than blood collection, can be used to assay buccal DNAm. This study examines how buccal-originated epigenetic clocks relate to socioeconomic status (SES) and health, and compares these associations to those of blood-originated clocks applied to buccal DNAm in the German SOEP cohort (N = 1,128, aged 0-72, 57% female). We found that, unlike second- and third-generation blood-originated clocks (PCPhenoAge, PCGrimAge, and DunedinPACE), a first-generation buccal-derived clock (PedBE acceleration) and a novel second-generation buccal-derived clock trained on age, lifestyle, and health factors (CheekAge acceleration) were not significantly correlated with SES. All clocks were associated with health, and those associations were similar in magnitude across buccal- and blood-originated clocks. Our findings suggest that PedBE and CheekAge acceleration did not show stronger associations with SES and health compared to blood-originated clocks. The finding that PedBE acceleration, which is trained on chronological age in 0-20-year-olds, was associated with self-reported health and had the strongest association with multimorbidity (without cancer) is consistent with the notion that the methylome captures health-relevant processes early in ontogeny. Future studies should include multiple tissue types to further evaluate whether buccal DNAm is sensitive to socioeconomic health disparities. The development of buccal clocks may benefit from further training on aging-related biomarkers and mortality, as well as longitudinal changes in biomarkers beginning early in ontogeny.