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

• Type of Material: Article
• Authors: Leanne K. Kupers, University of Bristol; Claire Monnereau, University Medical Center Rotterdam; Gemma C. Sharp, University of Bristol; Paul Yousefi, University of Bristol; Lucas A. Salas, Dartmouth College; Akram Ghantous, International Agency Research on Cancer; Christian M. Page, Norwegian Institute of Public Health; Sarah E. Reese, National Institutes of Health; Allen J. Wilcox, National Institutes of Health; Darina Czamara, Max-Planck-Institute of Psychiatry; Anne P. Starling, University of Colorado; Alexei Novoloaca, International Agency Research on Cancer; Samantha Lent, Boston University; Ritu Roy, University of California, San Francisco; Catherine Hoyo, North Carolina State University; Carrie V. Breton, University of Southern California; Catherine Allard, Centre Hospitalier Universitaire de Sherbrooke; Todd Everson, Emory University; Carmen Marsit, Emory University; Elisabeth Binder, Emory University
• Language: English
• Date: 2019-04-23
• Publisher: Nature Research (part of Springer Nature): Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-019-09671-3
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 10
• Issue: 1
• Start Page: 1893
• End Page: 1893
• Grant/Funding Information: Funding statements can be found in supplementary information.
• Keywords: MATERNAL SMOKING; PREGNANCY; CORD BLOOD; EPIGENETIC MEDIATION; PACKAGE; GENETIC-EVIDENCE; DISEASE; Science & Technology; MENDELIAN RANDOMIZATION; BIOCONDUCTOR; FETAL ORIGINS; Multidisciplinary Sciences; Science & Technology - Other Topics
• Research Categories: Health Sciences, Public Health; Health Sciences, Obstetrics and Gynecology; Health Sciences, Epidemiology

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 (P Bonferroni < 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.