Childhood growth and development and DNA methylation age in mid-life

Abstract

BackgroundIn the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life.MethodsParticipants were from the Medical Research Council National Survey of Health and Development(n=1,376). Four DNAm age acceleration(AgeAccel) biomarkers were measured when participants were aged 53y:AgeAccelHannum, AgeAccelHorvath, AgeAccelLevine and AgeAccelGrim. Exposure variables included relative weight gain (standardised residuals from models of current weight z-score on current height, and previous weight and height z-scores) and linear growth (standardised residuals from models of current height z-score on previous height and weight z-scores) during infancy (0-2y, weight gain only), early childhood(2-4y), middle childhood(4-7y) and late childhood to adolescence(7- 15y), age at menarche and pubertal stage for men at 14-15y. The relationship between relative weight gain and linear growth and AgeAccel was investigated using conditional growth models. We replicated analyses from the late childhood to adolescence period and pubertal timing among 240 participants from The National Child and Development Study(NCDS).ResultsA 1 SD increase in relative weight gain in late childhood to adolescence was associated with 0.50y(95% CI:0.20,0.79) higher AgeAccelGrim. This was replicated in NCDS (0.57y(95%CI:-0.01, 1.16). A I SD increase in linear growth during early childhood was associated with lower AgeAccelLevine(−0.39y [95% CI:-0.74,-0.04) however we did not have the data to replicate this finding in NCDS. There was no strong evidence that relative weight gain and linear growth in childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and AgeAccel biomarkers. Women who reached menarche ≥12y had 1.20y(95% CI:0.15,2.24) higher AgeAccelGrim on average than women who reached menarche <12y; however this was not replicated in NCDS.ConclusionsOur findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, rapid weight gain during pubertal development, which we found to be related to older AgeAccelGrim and had previously been related to higher cardiovascular disease risk, warrants further investigation.