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Publication - Professor Caroline Relton

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

    Citation

    Küpers, LK, Monnereau, C, Sharp, GC, Yousefi, P, Salas, LA, Ghantous, A, Page, CM, Reese, SE, Wilcox, AJ, Czamara, D, Starling, AP, Novoloaca, A, Lent, S, Roy, R, Hoyo, C, Breton, CV, Allard, C, Just, AC, Bakulski, KM, Holloway, JW, Everson, TM, Xu, CJ, Huang, RC, Plaat, DAvd, Wielscher, M, Merid, SK, Ullemar, V, Rezwan, FI, Lahti, J, van Dongen, J, Langie, SA, Richardson, TG, Magnus, MC, Nohr, EA, Xu, Z, Duijts, L, Zhao, S, Zhang, W, Plusquin, M, DeMeo, DL & others 2019, ‘Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight’. Nature Communications, vol 10.

    Abstract

    Birthweight is associated with health outcomes across the life course. DNA methylation may be an underlying mechanism in these associations. In a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohortsin the Pregnancy And Childhood Epigenetics Consortium, DNA methylation in neonatal blood was associated with birthweight at 955 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni<1.06x10-7 6 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation was also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlapped with some CpGs that were previously reported to be differentially methylated in relation to smoking56/955, penrichment=1.23x10-74) and BMI in pregnancy (3/955, penrichment=1.28x10-3 10 ), but not with those related to famine or folate levels in pregnancy. Neonatal DNA methylation is associated with birthweight, with some of the differentially methylated sites overlapping with those associated with intrauterine exposure to smoking and BMI. Whether the associations that we have observed are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

    Full details in the University publications repository