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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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posted on 2023-05-21, 01:29 authored by Kupers, 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, C-J, Huang, R-C, van der Plaat, DA, Wielscher, M, Merid, SK, Ullemar, V, Rezwan, FI, Lahti, J, van Dongen, J, Langie, SAS, Richardson, TG, Magnus, MC, Nohr, EA, Xu, Z, Duijts, L, Zhao, S, Zhang, W, Plusquin, M, DeMeo, DL, Solomon, O, Heimovaara, JH, Jima, DD, Gao, L, Bustamante, M, Perron, P, Wright, RO, Hertz-Picciotto, I, Zhang, H, Karagas, MR, Gehring, U, Marsit, CJ, Beilin, LJ, Vonk, JM, Jarvelin, M-R, Bergstrom, A, Ortqvist, AK, Ewart, S, Villa, PM, Moore, SE, Willemsen, G, Standaert, ARL, Haberg, SE, Sorensen, TIA, Taylor, JA, Raikkonen, K, Yang, IV, Kechris, K, Nawrot, TS, Silver, MJ, Gong, YY, Richiardi, L, Kogevinas, M, Litonjua, AA, Eskenazi, B, Huen, K, Mbarek, H, Maguire, RL, Dwyer, T, Vrijheid, M, Bouchard, L, Baccarelli, AA, Croen, LA, Karmaus, W, Anderson, D, de Vries, M, Sebert, S, Kere, J, Karlsson, R, Arshad, SH, Hamalainen, E, Routledge, MN, Boomsma, DI, Feinberg, AP, Newschaffer, CJ, Govarts, E, Moisse, M, Fallin, MD, Melen, E, Prentice, AM, Kajantie, E, Almqvist, C, Oken, E, Dabelea, D, Boezen, HM, Phillip MeltonPhillip Melton, Wright, RJ, Koppelman, GH, Trevisi, L, Hivert, M-F, Sunyer, J, Munthe-Kaas, MC, Murphy, SK, Corpeleijn, E, Wiemels, J, Holland, N, Herceg, Z, Binder, EB, Davey Smith, G, Jaddoe, VWV, Lie, RT, Nystad, W, London, SJ, Lawlor, DA, Relton, CL, Snieder, H, Felix, JF
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.

History

Publication title

Nature Communications

Volume

10

Article number

1893

Number

1893

Pagination

1-11

ISSN

2041-1723

Department/School

Menzies Institute for Medical Research

Publisher

Nature Pub. Group

Place of publication

United Kingdom

Rights statement

© 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.

Repository Status

  • Open

Socio-economic Objectives

Neonatal and child health

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