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

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Kupers, LK and Monnereau, C and Sharp, GC and Yousefi, P and Salas, LA and Ghantous, A and Page, CM and Reese, SE and Wilcox, AJ and Czamara, D and Starling, AP and Novoloaca, A and Lent, S and Roy, R and Hoyo, C and Breton, CV and Allard, C and Just, AC and Bakulski, KM and Holloway, JW and Everson, TM and Xu, C-J and Huang, R-C and van der Plaat, DA and Wielscher, M and Merid, SK and Ullemar, V and Rezwan, FI and Lahti, J and van Dongen, J and Langie, SAS and Richardson, TG and Magnus, MC and Nohr, EA and Xu, Z and Duijts, L and Zhao, S and Zhang, W and Plusquin, M and DeMeo, DL and Solomon, O and Heimovaara, JH and Jima, DD and Gao, L and Bustamante, M and Perron, P and Wright, RO and Hertz-Picciotto, I and Zhang, H and Karagas, MR and Gehring, U and Marsit, CJ and Beilin, LJ and Vonk, JM and Jarvelin, M-R and Bergstrom, A and Ortqvist, AK and Ewart, S and Villa, PM and Moore, SE and Willemsen, G and Standaert, ARL and Haberg, SE and Sorensen, TIA and Taylor, JA and Raikkonen, K and Yang, IV and Kechris, K and Nawrot, TS and Silver, MJ and Gong, YY and Richiardi, L and Kogevinas, M and Litonjua, AA and Eskenazi, B and Huen, K and Mbarek, H and Maguire, RL and Dwyer, T and Vrijheid, M and Bouchard, L and Baccarelli, AA and Croen, LA and Karmaus, W and Anderson, D and de Vries, M and Sebert, S and Kere, J and Karlsson, R and Arshad, SH and Hamalainen, E and Routledge, MN and Boomsma, DI and Feinberg, AP and Newschaffer, CJ and Govarts, E and Moisse, M and Fallin, MD and Melen, E and Prentice, AM and Kajantie, E and Almqvist, C and Oken, E and Dabelea, D and Boezen, HM and Melton, PE and Wright, RJ and Koppelman, GH and Trevisi, L and Hivert, M-F and Sunyer, J and Munthe-Kaas, MC and Murphy, SK and Corpeleijn, E and Wiemels, J and Holland, N and Herceg, Z and Binder, EB and Davey Smith, G and Jaddoe, VWV and Lie, RT and Nystad, W and London, SJ and Lawlor, DA and Relton, CL and Snieder, H and Felix, JF, Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight, Nature Communications, 10, (1) pp. 1-11. ISSN 2041-1723 (2019) [Refereed Article]


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The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, (http://creativecommons.org/licenses/by/4.0/.) which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

DOI: doi:10.1038/s41467-019-09671-3

Abstract

Birthweight 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.

Item Details

Item Type:Refereed Article
Keywords:DNA methylation, birthweight, meta-analysis
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. genome methylation and epigenomics)
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Neonatal and child health
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:145923
Year Published:2019
Web of Science® Times Cited:63
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-08-12
Last Modified:2021-09-01
Downloads:6 View Download Statistics

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