Epigenetic age acceleration and cardiovascular outcomes in school-age children: The Generation R Study

Clinical Epigenetics

Vincent W. V. Jaddoe¹  Giulietta S. Monasso¹  Janine F. Felix¹  Leanne K. Küpers² 

[1]The Generation R Study Group (Na-2918), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[2]Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[3]The Generation R Study Group (Na-2918), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[4]Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[5]Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands

关键词: DNA methylation;    Epigenetic clock;    Gestational age;    Cohort study;    Cardiovascular disease;    Carotid intima-media thickness;    Atherosclerosis;    Distensibility;   

DOI  :  10.1186/s13148-021-01193-4

来源: Springer

【 摘 要 】

BackgroundHypertension and atherosclerosis may partly originate in early life. Altered epigenetic aging may be a mechanism underlying associations of early-life exposures and the development of cardiovascular risk factors in childhood. A discrepancy between chronological age and age predicted from neonatal DNA methylation data is referred to as age acceleration. It may either be positive, if DNA methylation age is older than clinical age, or negative, if DNA methylation age is younger than chronological age. We examined associations of age acceleration at birth (‘gestational age acceleration’), and of age acceleration at school-age, with blood pressure and with intima-media thickness and distensibility of the common carotid artery, as markers of vascular structure and function, respectively, measured at age 10 years.ResultsThis study was embedded in the Generation R Study, a population-based prospective cohort study. We included 1115 children with information on cord blood DNA methylation and blood pressure, carotid intima-media thickness or carotid distensibility. Gestational age acceleration was calculated using the Bohlin epigenetic clock, which was developed specifically for cord blood DNA methylation data. It predicts gestational age based on methylation levels of 96 CpGs from HumanMethylation450 BeadChip. We observed no associations of gestational age acceleration with blood pressure, carotid intima-media thickness or carotid distensibility at age 10 years. In analyses among children with peripheral blood DNA methylation measured at age 6 (n = 470) and 10 (n = 449) years, we also observed no associations of age acceleration at these ages with the same cardiovascular outcomes, using the ‘skin and blood clock,’ which predicts age based on methylation levels at 391 CpGs from HumanMethylation450 BeadChip.ConclusionsOur findings do not provide support for the hypothesis that altered epigenetic aging during the earliest phase of life is involved in the development of cardiovascular risk factors in childhood.

【 授权许可】

CC BY