Published in

Nature Research, Nature Communications, 1(10), 2019

DOI: 10.1038/s41467-019-09671-3

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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Journal article published in 2019 by Leanne K. Küpers, Claire Monnereau, Gemma C. Sharp ORCID, Paul Yousefi, Lucas A. Salas ORCID, Akram Ghantous, Christian M. Page, Sarah E. Reese, Allen J. Wilcox, Darina Czamara ORCID, Anne P. Starling, Alexei Novoloaca, Samantha Lent, Ritu Roy, Cathrine Hoyo and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

AbstractBirthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.