TY - JOUR 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 DO - 10.1101/125492 SP - 125492 AU - Gemma C Sharp AU - Lucas A Salas AU - Claire Monnereau AU - Catherine Allard AU - Paul Yousefi AU - Todd M Everson AU - Jon Bohlin AU - Zongli Xu AU - Rae-Chi Huang AU - Sarah E Reese AU - Cheng-Jian Xu AU - Nour Baïz AU - Cathrine Hoyo AU - Golareh Agha AU - Ritu Roy AU - John W Holloway AU - Akram Ghantous AU - Simon Kebede Merid AU - Kelly M Bakulski AU - Leanne K Küpers AU - Hongmei Zhang AU - Rebecca C Richmond AU - Christian M Page AU - Liesbeth Duijts AU - Rolv T Lie AU - Phillip E Melton AU - Judith M Vonk AU - Ellen A Nohr AU - CharLynda Williams-DeVane AU - Karen Huen AU - Sheryl L Rifas-Shiman AU - Carlos Ruiz-Arenas AU - Semira Gonseth AU - Faisal I Rezwan AU - Zdenko Herceg AU - Sandra Ekström AU - Lisa Croen AU - Fahimeh Falahi AU - Patrice Perron AU - Margaret R Karagas AU - Bilal Mohammed Quraishi AU - Matthew Suderman AU - Maria C Magnus AU - Vincent WV Jaddoe AU - Jack A Taylor AU - Denise Anderson AU - Shanshan Zhao AU - Henriette A Smit AU - Michele J Josey AU - Asa Bradman AU - Andrea A Baccarelli AU - Mariona Bustamante AU - Siri E Håberg AU - Göran Pershagen AU - Irva Hertz-Picciotto AU - Craig Newschaffer AU - Eva Corpeleijn AU - Luigi Bouchard AU - Debbie A Lawlor AU - Rachel L Maguire AU - Lisa F Barcellos AU - George Davey Smith AU - Brenda Eskenazi AU - Wilfried Karmaus AU - Carmen J Marsit AU - Marie-France Hivert AU - Harold Snieder AU - M Daniele Fallin AU - Erik Melén AU - Monica C Munthe-Kaas AU - Hasan Arshad AU - Joseph L Wiemels AU - Isabella Annesi-Maesano AU - Martine Vrijheid AU - Emily Oken AU - Nina Holland AU - Susan K Murphy AU - Thorkild IA Sørensen AU - Gerard H Koppelman AU - John P Newnham AU - Allen J Wilcox AU - Wenche Nystad AU - Stephanie J London AU - Janine F Felix AU - Caroline L Relton Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/13/125492.abstract N2 - 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. ER -