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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


Sharp, GC and Salas, LA and Monnereau, C and Allard, C and Yousefi, P and Everson, TM and Bohlin, J and Xu, Z and Huang, R-C and Reese, SE and Xu, C-J and Baiz, N and Hoyo, C and Agha, G and Roy, R and Holloway, JW and Ghantous, A and Merid, SK and Bakulski, KM and Kupers, LK and Zhang, H and Richmond, RC and Page, CM and Duijts, L and Lie, RT and Melton, PE and Vonk, JM and Nohr, EA and Williams-DeVane, C and Huen, K and Rifas-Shiman, SL and Ruiz-Arenas, C and Gonseth, S and Rezwan, FI and Herceg, Z and Ekstrom, S and Croen, L and Falahi, F and Perron, P and Karagas, MR and Quraishi, BM and Suderman, M and Magnus, MC and Jaddoe, VWV and Taylor, JA and Anderson, D and Zhao, S and Smit, HA and Josey, MJ and Bradman, A and Baccarelli, AA and Bustamante, M and Haberg, SE and Pershagen, G and Hertz-Picciotto, I and Newschaffer, C and Corpeleijn, E and Bouchard, L and Lawlor, DA and Maguire, RL and Barcellos, LF and Smith, GD and Eskenazi, B and Karmaus, W and Marsit, CJ and Hivert, M-F and Snieder, H and Fallin, MD and Melen, E and Munthe-Kaas, MC and Arshad, H and Wiemels, JL and Annesi-Maesano, I and Vrijheid, M and Oken, E and Holland, N and Murphy, SK and Sorensen, TIA and Koppelman, GH and Newnham, JP and Wilcox, AJ and Nystad, W and London, SJ and Felix, JF and Relton, CL, Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the pregnancy and childhood epigenetics (PACE) consortium, Human Molecular Genetics, 26, (20) pp. 4067-4085. ISSN 0964-6906 (2017) [Refereed Article]

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VC The Author 2017. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: doi:10.1093/hmg/ddx290


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/m2), 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 acausal 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.

Item Details

Item Type:Refereed Article
Keywords:DNA methylation, maternal BMI, meta-analysis
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. genome methylation and epigenomics)
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Neonatal and child health
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:144628
Year Published:2017
Web of Science® Times Cited:108
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-05-31
Last Modified:2021-06-02
Downloads:9 View Download Statistics

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