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

Authors:
Leanne K Küpers Claire Monnereau Gemma C Sharp Paul Yousefi Lucas A Salas Akram Ghantous Christian M Page Sarah E Reese Allen J Wilcox Darina Czamara Anne P Starling Alexei Novoloaca Samantha Lent Ritu Roy Cathrine Hoyo Carrie V Breton Catherine Allard Allan C Just Kelly M Bakulski John W Holloway Todd M Everson Cheng-Jian Xu Rae-Chi Huang Diana A van der Plaat Matthias Wielscher Simon Kebede Merid Vilhelmina Ullemar Faisal I Rezwan Jari Lahti Jenny van Dongen Sabine A S Langie Tom G Richardson Maria C Magnus Ellen A Nohr Zongli Xu Liesbeth Duijts Shanshan Zhao Weiming Zhang Michelle Plusquin Dawn L DeMeo Olivia Solomon Joosje H Heimovaara Dereje D Jima Lu Gao Mariona Bustamante Patrice Perron Robert O Wright Irva Hertz-Picciotto Hongmei Zhang Margaret R Karagas Ulrike Gehring Carmen J Marsit Lawrence J Beilin Judith M Vonk Marjo-Riitta Jarvelin Anna Bergström Anne K Örtqvist Susan Ewart Pia M Villa Sophie E Moore Gonneke Willemsen Arnout R L Standaert Siri E Håberg Thorkild I A Sørensen Jack A Taylor Katri Räikkönen Ivana V Yang Katerina Kechris Tim S Nawrot Matt J Silver Yun Yun Gong Lorenzo Richiardi Manolis Kogevinas Augusto A Litonjua Brenda Eskenazi Karen Huen Hamdi Mbarek Rachel L Maguire Terence Dwyer Martine Vrijheid Luigi Bouchard Andrea A Baccarelli Lisa A Croen Wilfried Karmaus Denise Anderson Maaike de Vries Sylvain Sebert Juha Kere Robert Karlsson Syed Hasan Arshad Esa Hämäläinen Michael N Routledge Dorret I Boomsma Andrew P Feinberg Craig J Newschaffer Eva Govarts Matthieu Moisse M Daniele Fallin Erik Melén Andrew M Prentice Eero Kajantie Catarina Almqvist Emily Oken Dana Dabelea H Marike Boezen Phillip E Melton Rosalind J Wright Gerard H Koppelman Letizia Trevisi Marie-France Hivert Jordi Sunyer Monica C Munthe-Kaas Susan K Murphy Eva Corpeleijn Joseph Wiemels Nina Holland Zdenko Herceg Elisabeth B Binder George Davey Smith Vincent W V Jaddoe Rolv T Lie Wenche Nystad Stephanie J London Debbie A Lawlor Caroline L Relton Harold Snieder Janine F Felix

Nat Commun 2019 04 23;10(1):1893. Epub 2019 Apr 23.

The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

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 (P < 1.06 x 10). 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) and BMI in pregnancy (3/914, p = 1.13x10), 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.

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http://dx.doi.org/10.1038/s41467-019-09671-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478731PMC
April 2019
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