Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
Kupers, Leanne K.; Monnereau, Claire; Sharp, Gemma C.; Yousefi, Paul; Salas, Lucas A.; Ghantous, Akram; Page, Christian M.; Reese, Sarah E.; Wilcox, Allen J.; Czamara, Darina; Starling, Anne P.; Novoloaca, Alexei; Lent, Samantha; Roy, Ritu; Hoyo, Cathrine; Breton, Carrie, V; Allard, Catherine; Just, Allan C.; Bakulski, Kelly M.; Holloway, John W.; Everson, Todd M.; Xu, Cheng-Jian; Huang, Rae-Chi; van der Plaat, Diana A.; Wielscher, Matthias; Merid, Simon Kebede; Ullemar, Vilhelmina; Rezwan, Faisal, I; Lahti, Jari; van Dongen, Jenny; Langie, Sabine A. S.; Richardson, Tom G.; Magnus, Maria C.; Nohr, Ellen A.; Xu, Zongli; Duijts, Liesbeth; Zhao, Shanshan; Zhang, Weiming; Plusquin, Michelle; DeMeo, Dawn L.; Solomon, Olivia; Heimovaara, Joosje H.; Jima, Dereje D.; Gao, Lu; Bustamante, Mariona; Perron, Patrice; Wright, Robert O.; Hertz-Picciotto, Irva; Zhang, Hongmei; Karagas, Margaret R.; Gehring, Ulrike; Marsit, Carmen J.; Beilin, Lawrence J.; Vonk, Judith M.; Järvelin, Marjo-Riitta; Bergstrom, Anna; Ortqvist, Anne K.; Ewart, Susan; Villa, Pia M.; Moore, Sophie E.; Willemsen, Gonneke; Standaert, Arnout R. L.; Haberg, Siri E.; Sorensen, Thorkild I. A.; Taylor, Jack A.; Raikkonen, Katri; Yang, Ivana, V; Kechris, Katerina; Nawrot, Tim S.; Silver, Matt J.; Gong, Yun Yun; Richiardi, Lorenzo; Kogevinas, Manolis; Litonjua, Augusto A.; Eskenazi, Brenda; Huen, Karen; Mbarek, Hamdi; Maguire, Rachel L.; Dwyer, Terence; Vrijheid, Martine; Bouchard, Luigi; Baccarelli, Andrea A.; Croen, Lisa A.; Karmaus, Wilfried; Anderson, Denise; de Vries, Maaike; Sebert, Sylvain; Kere, Juha; Karlsson, Robert; Arshad, Syed Hasan; Hamalainen, Esa; Routledge, Michael N.; Boomsma, Dorret, I; Feinberg, Andrew P.; Newschaffer, Craig J.; Govarts, Eva; Moisse, Matthieu; Fallin, M. Daniele; Melen, Erik; Prentice, Andrew M.; Kajantie, Eero; Almqvist, Catarina; Oken, Emily; Dabelea, Dana; Boezen, H. Marike; Melton, Phillip E.; Wright, Rosalind J.; Koppelman, Gerard H.; Trevisi, Letizia; Hivert, Marie-France; Sunyer, Jordi; Munthe-Kaas, Monica C.; Murphy, Susan K.; Corpeleijn, Eva; Wiemels, Joseph; Holland, Nina; Herceg, Zdenko; Binder, Elisabeth B.; Smith, George Davey; Jaddoe, Vincent W. V.; Lie, Rolv T.; Nystad, Wenche; London, Stephanie J.; Lawlor, Debbie A.; Relton, Caroline L.; Snieder, Harold; Felix, Janine F. (2019-04-23)
Küpers, L.K., Monnereau, C., Sharp, G.C. et al. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight. Nat Commun 10, 1893 (2019). https://doi.org/10.1038/s41467-019-09671-3
© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe2020042822771
Tiivistelmä
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.
Kokoelmat
- Avoin saatavuus [34196]
