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Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium

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  • 03/05/2025
Type of Material
Authors
    Gemma C. Sharp, University of BristolLucas A. Salas, Centre for Research in Environmental EpidemiologyClaire Monnereau, University Medical Center RotterdamCatherine Allard, Université de SherbrookePaul Yousefi, University of California BerkeleyTodd M. Everson, Emory UniversityJon Bohlin, Norwegian Institute of Public HealthZongli Xu, National Institutes of HealthRae-Chi Huang, University of Western AustraliaSarah E. Reese, National Institutes of HealthCheng-Jian Xu, University of GroningenNour Baiz, Sorbonne UniversitéCatherine Hoyo, North Carolina State UniversityGolareh Agha, Columbia UniversityRilu Roy, University of California San FranciscoJohn W. Holloway, University of SouthamptonAkram Ghantous, International Agency for Research on CancerSimon K. Merid, Karolinska InstitutetKelly M. Bakulski, University of MichiganLeanne K. Kupers, University of BristolHongmei Zhang, University of MemphisRebecca C. Richmond, University of BristolChristian M. Page, Norwegian Institute of Public HealthLiesbeth Duijts, University Medical Center RotterdamRolv T. Lie, University of BergenPhillip E. Melton, University of Western AustraliaJudith M. Vonk, University of GroningenEllen A. Nohr, University of Southern DenmarkClarLynda Williams-DeVane, North Carolina Central UniversityKaren Huen, University of California BerkeleySheryl l. Rifas-Shiman, Harvard Medical SchoolCarlos Ruiz-Arenas, Centre for Research in Environmental EpidemiologySemira Gonseth, University of California San FranciscoFaisal I. Rezwan, University of SouthamptonZdenko Herceg, International Agency for Research on CancerSandra Ekstrom, Karolinska InstitutetLisa Croen, International Agency for Research on CancerFahimeh Falahi, University of GroningenPatrice Perron, University of SherbrookeMargaret R. Karagas, Geisel School of Medicine at DartmouthBilal M. Quraishi, University of MemphisMatthew Suderman, University of BristolMaria C. Magnus, University of BristolVincent W. V. Jaddoe, University Medical Center RotterdamJack A. Taylor, National Institutes of HealthDenise Anderson, University of Western AustraliaShanshan Zhao, University of Western AustraliaHenriette A. Smit, University Medical Center UtrechtMichele J. Josey, North Carolina Central UniversityAsa Bradman, University of California BerkeleyAndrea A. Baccarelli, Columbia UniversityMariona Bustamante, Centre for Research in Environmental EpidemiologySiri E. Haberg, Norwegian Institute of Public HealthGoran Pershagen, Karolinska InstitutetIrva Hertz-Picciotto, University of California DavisCraig Newschaffer, Drexel UniversityEva Corpeleijn, University of GroningenLuigi Bouchard, University of SherbrookeDebbie A. Lawlor, University of BristolRachel L. Maguire, North Carolina State UniversityLisa F. Barcellos, University of California BerkeleyGeorge Davey Smith, University of BristolBrenda Eskenazi, University of California BerkeleyWilfried Karmaus, University of GroningenCarmen Marsit, Emory UniversityMarie-France Hivert, Harvard Medical SchoolHarold Snieder, University of GroningenM. Daniele Fallin, Johns Hopkins UniversityErik Melen, Karolinska InstitutetMonica C. Munthe-Kaas, Oslo University HospitalHasan Arshad, University of SouthamptonJoseph L. Wiemels, University of California San FranciscoIsabella Annesi-Maesano, Sorbonne UniversitéMartine Vrijheid, Centre for Research in Environmental EpidemiologyEmily Oken, Harvard Medical SchoolNina Holland, University of California BerkeleySusan K. Murphy, Duke UniversityThorkild I. A. Sorensen, University of BristolGerard H. Koppelman, University of GroningenJohn P. Newnham, University of Western AustraliaAllen J. Wilcox, National Institutes of HealthWenche Nystad, Norwegian Institute of Public HealthStephanie J. London, National Institutes of HealthJanine F. Felix, University Medical Center RotterdamCaroline L. Relton, University of Bristol
Language
  • English
Date
  • 2017-10-15
Publisher
  • Oxford University Press (OUP): Policy B - Oxford Open Option B
Publication Version
Copyright Statement
  • © The Author 2017. Published by Oxford University Press. All rights reserved.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 0964-6906
Volume
  • 26
Issue
  • 20
Start Page
  • 4067
End Page
  • 4085
Grant/Funding Information
  • Funding to pay the open access publication charges for this article was provided by the Open Access Library Services at the University of Bristol.
  • For all studies, funding information can be found in the Supplementary Material
Supplemental Material (URL)
Abstract
  • Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. 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 the 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 small ( < 0.2% per BMI unit (1 kg/m 2 ), P < 1.06 × 10 -7 ) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for a6causal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.
Author Notes
  • To whom correspondence should be addressed at: MRC Integrative Epidemiology Unit, University of Bristol, Barley House, Oakfield Grove, Bristol BS8 2BN, UK. Tel: +44 (0)117 331 0098; gemma.sharp@bristol.ac.uk.
Keywords
Research Categories
  • Health Sciences, Public Health
  • Environmental Sciences

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