An epigenetic clock for gestational age based on human umbilical vein endothelial cells from a diverse population of newborns

Abstract

Background: Epigenetic clocks are emerging as a useful tool in many areas of research. Many epigenetic clocks have been developed for adults; however, there are fewer clocks focused on newborns and most are trained using blood from European ancestry populations. In this study, we built an epigenetic clock based on primary human umbilical vein endothelial cells from a racially and ethnically diverse population. Results: Using human umbilical vein endothelial cell [HUVEC]-derived DNA, we calculated epigenetic gestational age using 83 CpG sites selected through elastic net regression. In this study with newborns from different racial/ethnic identities, epigenetic gestational age and clinical gestational age were more highly correlated (r = 0.85), than epigenetic clocks built from adult and other pediatric populations. The correlation was also higher than clocks based on blood samples from newborns with European ancestry. We also found that birth weight was positively associated with epigenetic gestational age acceleration (EGAA), while NICU admission was associated with lower EGAA. Newborns self-identified as Hispanic or non-Hispanic Black had lower EGAA than self-identified as non-Hispanic White. Conclusions: Epigenetic gestational age can be used to estimate clinical gestational age and may help index neonatal development. Caution should be exercised when using epigenetic clocks built from adults with children, especially newborns. We highlight the importance of cell type-specific epigenetic clocks and general pan tissue epigenetic clocks derived from a large racially and ethnically diverse population.