RT Journal Article
SR Electronic
T1 Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 125492
DO 10.1101/125492
A1 Gemma C Sharp
A1 Lucas A Salas
A1 Claire Monnereau
A1 Catherine Allard
A1 Paul Yousefi
A1 Todd M Everson
A1 Jon Bohlin
A1 Zongli Xu
A1 Rae-Chi Huang
A1 Sarah E Reese
A1 Cheng-Jian Xu
A1 Nour Baïz
A1 Cathrine Hoyo
A1 Golareh Agha
A1 Ritu Roy
A1 John W Holloway
A1 Akram Ghantous
A1 Simon Kebede Merid
A1 Kelly M Bakulski
A1 Leanne K Küpers
A1 Hongmei Zhang
A1 Rebecca C Richmond
A1 Christian M Page
A1 Liesbeth Duijts
A1 Rolv T Lie
A1 Phillip E Melton
A1 Judith M Vonk
A1 Ellen A Nohr
A1 CharLynda Williams-DeVane
A1 Karen Huen
A1 Sheryl L Rifas-Shiman
A1 Carlos Ruiz-Arenas
A1 Semira Gonseth
A1 Faisal I Rezwan
A1 Zdenko Herceg
A1 Sandra Ekström
A1 Lisa Croen
A1 Fahimeh Falahi
A1 Patrice Perron
A1 Margaret R Karagas
A1 Bilal Mohammed Quraishi
A1 Matthew Suderman
A1 Maria C Magnus
A1 Vincent WV Jaddoe
A1 Jack A Taylor
A1 Denise Anderson
A1 Shanshan Zhao
A1 Henriette A Smit
A1 Michele J Josey
A1 Asa Bradman
A1 Andrea A Baccarelli
A1 Mariona Bustamante
A1 Siri E Håberg
A1 Göran Pershagen
A1 Irva Hertz-Picciotto
A1 Craig Newschaffer
A1 Eva Corpeleijn
A1 Luigi Bouchard
A1 Debbie A Lawlor
A1 Rachel L Maguire
A1 Lisa F Barcellos
A1 George Davey Smith
A1 Brenda Eskenazi
A1 Wilfried Karmaus
A1 Carmen J Marsit
A1 Marie-France Hivert
A1 Harold Sniede
A1 M Daniele Fallin
A1 Erik Melén
A1 Monica C Munthe-Kaas
A1 Hasan Arshad
A1 Joseph L Wiemels
A1 Isabella Annesi-Maesano
A1 Martine Vrijheid
A1 Emily Oken
A1 Nina Holland
A1 Susan K Murphy
A1 Thorkild IA Sørensen
A1 Gerard H Koppelman
A1 John P Newnham
A1 Allen J Wilcox
A1 Wenche Nystad
A1 Stephanie J London
A1 Janine F Felix
A1 Caroline L Relton
YR 2017
UL http://biorxiv.org/content/early/2017/04/13/125492.1.abstract
AB Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Epigenetic modifications such as DNA methylation could contribute, but data are scarce.Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents.In newborns, maternal BMI was associated with modest (<0.2% per BMI unit (1kg/m2), P<1.06*10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. These 86 sites map to several genes reported to be associated with adiposity-related and/or neuropsychiatric traits. At 72/86 sites, the direction of association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for a causal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites.In conclusion, maternal adiposity is associated with modest variations in newborn blood DNA methylation, but the potential biological consequences of these variations are currently unclear.