Epigenetic clocks derived from western samples differentially reflect Taiwanese health outcomes

Introduction: Several epigenetic clocks have been developed, with five measures of epigenetic age acceleration (EAA) especially receiving extensive investigations: HannumEAA, IEAA, PhenoEAA, GrimEAA, and DunedinPACE. These epigenetic clocks were mainly developed by individuals of European or Hispanic ancestry. It remains unclear whether they can reflect disease morbidity and physiological conditions in Asian populations. Methods: I here investigated five measures of EAA of 2,474 Taiwan Biobank participants with DNA methylation data. Using logistic regressions, I sequentially regressed various health outcomes on each of the five measures of EAA while adjusting for chronological age, sex, body mass index, the number of smoking pack-years, drinking status, regular exercise, educational attainment, and six cell-type proportions. Results: Except for IEAA, all measures of EAA reflected the obesity of Taiwanese (p < 4.0E-4). Diabetes was reflected by DunedinPACE (p = 5.4E-6) and GrimEAA (p = 5.8E-5). Moreover, DunedinPACE was associated with dyslipidemia, including hypertriglyceridemia (p = 1.1E-5), low high-density lipoprotein cholesterol (HDL-C) (p = 4.0E-5), and high triglyceride to HDL-C ratio (p = 1.6E-7). Discussion: This is one of the first studies to show that epigenetic clocks (developed by individuals of European or Hispanic ancestry) can reflect Taiwanese physiological conditions. DunedinPACE was associated with more Taiwanese health outcomes than the other four measures of EAA.