@article {Sharp125492, author = {Gemma C Sharp and Lucas A Salas and Claire Monnereau and Catherine Allard and Paul Yousefi and Todd M Everson and Jon Bohlin and Zongli Xu and Rae-Chi Huang and Sarah E Reese and Cheng-Jian Xu and Nour Ba{\"\i}z and Cathrine Hoyo and Golareh Agha and Ritu Roy and John W Holloway and Akram Ghantous and Simon Kebede Merid and Kelly M Bakulski and Leanne K K{\"u}pers and Hongmei Zhang and Rebecca C Richmond and Christian M Page and Liesbeth Duijts and Rolv T Lie and Phillip E Melton and Judith M Vonk and Ellen A Nohr and CharLynda Williams-DeVane and Karen Huen and Sheryl L Rifas-Shiman and Carlos Ruiz-Arenas and Semira Gonseth and Faisal I Rezwan and Zdenko Herceg and Sandra Ekstr{\"o}m and Lisa Croen and Fahimeh Falahi and Patrice Perron and Margaret R Karagas and Bilal Mohammed Quraishi and Matthew Suderman and Maria C Magnus and Vincent WV Jaddoe and Jack A Taylor and Denise Anderson and Shanshan Zhao and Henriette A Smit and Michele J Josey and Asa Bradman and Andrea A Baccarelli and Mariona Bustamante and Siri E H{\r a}berg and G{\"o}ran Pershagen and Irva Hertz-Picciotto and Craig Newschaffer and Eva Corpeleijn and Luigi Bouchard and Debbie A Lawlor and Rachel L Maguire and Lisa F Barcellos and George Davey Smith and Brenda Eskenazi and Wilfried Karmaus and Carmen J Marsit and Marie-France Hivert and Harold Sniede and M Daniele Fallin and Erik Mel{\'e}n and Monica C Munthe-Kaas and Hasan Arshad and Joseph L Wiemels and Isabella Annesi-Maesano and Martine Vrijheid and Emily Oken and Nina Holland and Susan K Murphy and Thorkild IA S{\o}rensen and Gerard H Koppelman and John P Newnham and Allen J Wilcox and Wenche Nystad and Stephanie J London and Janine F Felix and Caroline L Relton}, title = {Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium}, elocation-id = {125492}, year = {2017}, doi = {10.1101/125492}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2017/04/13/125492.1}, eprint = {https://www.biorxiv.org/content/early/2017/04/13/125492.1.full.pdf}, journal = {bioRxiv} }