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

Research output: Contribution to journalArticlepeer-review

Jane Maddock, Juan Castillo-Fernandez, Andrew Wong, George B. Ploubidis, Diana Kuh, Jordana T. Bell, Rebecca Hardy

Original languageEnglish
Article number155
JournalClinical Epigenetics
Volume13
Issue number1
DOIs
PublishedDec 2021

Bibliographical note

Funding Information: This work was supported by the Economic and Social Research Council/Biotechnology and Biological Sciences Research Council [ES/N000404/1]. The UK Medical Research Council provides core funding for the MRC National Survey of Health and Development [MC_UU_00019/1]. RH is Director of CLOSER which is funded by the Economic and Social Research Council (award reference: ES/K000357/1). Funding Information: We thank NSHD and NCDS study members for their lifelong participation and past and present members of the study teams, including Professor Alissa Goodman, Professor Ken Ong and members of the MRC Epidemiology unit in Cambridge, who helped to collect and process the data. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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Abstract

Background: In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life. Methods: Participants were from the Medical Research Council National Survey of Health and Development (n = 1376). Four DNAm age acceleration (AgeAccel) biomarkers were measured when participants were aged 53 years: 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 (0–2 years, weight gain only), early childhood (2–4 years), middle childhood (4–7 years) and late childhood to adolescence (7–15 years); age at menarche; and pubertal stage for men at 14–15 years. 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). Results: A 1SD increase in relative weight gain in late childhood to adolescence was associated with 0.50 years (95% CI 0.20, 0.79) higher AgeAccelGrim. Although the CI includes the null, the estimate was similar in NCDS [0.57 years (95% CI − 0.01, 1.16)] 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 ≥ 12 years had 1.20 years (95% CI 0.15, 2.24) higher AgeAccelGrim on average than women who reached menarche < 12 years; however, this was not replicated in NCDS and was not statistically significant after Bonferroni correction. Conclusions: Our findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, we found rapid weight gain during pubertal development, previously related to higher cardiovascular disease risk, to be associated with older AgeAccelGrim. Given this is an exploratory study, this finding requires replication.

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