What’s counted counts: the implications of underrepresentation for the application of epigenetic clocks in diverse populations

Abstract

DNA methylation (DNAm) has been touted as a potential unified marker of the contributions of both inherited and environmental factors on an individual’s health. Changes in DNAm have been associated with several chronic diseases and mortality, and DNAm risk scores, or epigenetic clocks, have been proposed as metrics to quantify the process of ‘biological ageing’. Unfortunately, research involving epigenetic clocks is not free from the issues faced in other fields of genomic research. Namely, individuals of European ancestry make up the vast majority of epigenetic study participants and it is unclear whether epigenetic clocks will provide equitable benefits when applied in diverse populations. Although some studies have reported variation in DNAm between populations, it can be difficult to identify the mechanisms underlying these differences. This has implications for clinical application of epigenetic clocks. In this review, we discuss epigenetic clocks, missing diversity in epigenetic research and the potential consequences of the latter on the equitable translation of epigenetic clocks to diverse populations.