Associations of epigenetic age acceleration at birth and age 12 years with adolescent cardiometabolic risk: the HOME study

Abstract

Background: Cardiometabolic risk factors among youth are rising. Epigenetic age acceleration, a biomarker for aging and disease-risk, has been associated with adiposity in children, but its association with other cardiometabolic risk markers remains understudied. We employed data from the Health Outcomes and Measures of the Environment (HOME) study, a prospective pregnancy and birth cohort in the greater Cincinnati metropolitan area, to examine whether accelerated epigenetic age at birth as well as accelerated epigenetic age and faster pace of biological aging at age 12 years were associated with higher cardiometabolic risk in adolescents.

Results: After adjusting for potential confounders, including estimated cell type proportions, epigenetic gestational age acceleration at birth, derived from the Bohlin, Knight, and Haftorn clocks using cord blood DNA methylation data, was not associated with cardiometabolic risk z-scores or individual cardiometabolic risk score components (visceral fat, leptin to adiponectin ratio, HOMA-IR, triglycerides to HDL-C ratio, HbA1c, or systolic blood pressure) at age 12 years. We also did not observe any associations of epigenetic age acceleration, calculated with Horvath's skin and blood, Hannum's, and Wu's epigenetic clocks using peripheral blood at age 12 years, with these same cardiometabolic risk markers. In contrast, faster pace of biological aging was associated with higher cardiometabolic risk [βs (95% CIs)] cardiometabolic risk score 0.25 (0.07, 0.42); visceral fat 0.21 (0.05, 0.38); and hemoglobin A1c 0.23 (0.05, 0.41) per standard deviation increase in pace of biological aging. Faster pace of biological aging was also positively associated with systolic blood pressure, triglycerides to HDL-C ratio, HOMA-IR, and leptin to adiponectin ratio, although these associations were not statistically significant.

Conclusions: Our findings provide evidence that faster pace of biological aging was associated with higher cardiometabolic risk score, visceral fat, and HbA1c at age 12 years. Further research is needed to determine whether these associations persist from adolescence through adulthood.

Keywords: Adolescence; Cardiometabolic risk; Developmental origins of health and disease; Epidemiology; Epigenetic age.

Fig. 1

Spearman rank correlations of gestational age and epigenetic gestational age at birth (weeks) among singleton children from the HOME study (N = 181)

Fig. 2

Spearman rank correlations of chronological age and epigenetic age (years) at age 12 years among singleton children from the HOME study (N = 183)

Fig. 3

Spearman rank correlations of epigenetic gestational age acceleration (EGAA) at birth with epigenetic age acceleration (EAA) and pace of biological aging at age 12 years, among singleton children from the HOME study with DNA methylation data at birth and age 12 years (N = 152)

Fig. 4

Adjusted associations of intrinsic epigenetic gestational age acceleration (EGAA) at birth, and epigenetic age acceleration (EAA) and pace of biological aging at 12 years with adolescent cardiometabolic risk