Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.
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Paul Yousefi;
Lucas A Salas ;
Akram Ghantous;
Christian M Page;
Sarah E Reese;
Allen J Wilcox;
Darina Czamara ;
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Anne P Starling;
Alexei Novoloaca;
Samantha Lent;
Ritu Roy;
Cathrine Hoyo;
Carrie V Breton;
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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 AS Langie;
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Michelle Plusquin;
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Olivia Solomon;
Joosje H Heimovaara;
Dereje D Jima;
Lu Gao;
Mariona Bustamante;
Patrice Perron;
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Irva Hertz-Picciotto;
Hongmei Zhang;
Margaret R Karagas;
Ulrike Gehring;
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Judith M Vonk;
Marjo-Riitta Jarvelin;
Anna Bergström;
Anne K Örtqvist;
Susan Ewart;
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Sophie E Moore;
Gonneke Willemsen;
Arnout RL Standaert;
Siri E Håberg;
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Lorenzo Richiardi;
Manolis Kogevinas;
Augusto A Litonjua;
Brenda Eskenazi;
Karen Huen;
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Rachel L Maguire;
Terence Dwyer;
Martine Vrijheid;
Luigi Bouchard;
Andrea A Baccarelli;
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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;
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M Daniele Fallin;
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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 WV Jaddoe ;
Rolv T Lie;
Wenche Nystad;
Stephanie J London ;
Debbie A Lawlor ;
Caroline L Relton ;
Harold Snieder;
Janine F Felix ;
(2019)
Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.
NATURE COMMUNICATIONS, 10 (1).
1893-.
ISSN 2041-1723
DOI: 10.1038/s41467-019-09671-3
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.
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