Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the pregnancy and childhood epigenetics (PACE) consortium
MetadataShow full item record
© The Author 2017. Published by Oxford University Press. All rights reserved. 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.
Showing items related by title, author, creator and subject.
Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4Fransquet, P.; Hutchinson, D.; Olsson, C.; Allsop, Steve; Elliott, E.; Burns, L.; Mattick, R.; Saffery, R.; Ryan, J. (2017)Background: Maternal cannabis use in pregnancy is linked with long-term adverse behavioral outcomes in offspring. Epigenetic processes established in utero that affect dopaminergic (reward) signaling may mediate risks. ...
Reese, S.; Xu, C.; den Dekker, H.; Lee, M.; Sikdar, S.; Ruiz-Arenas, C.; Merid, S.; Rezwan, F.; Page, C.; Ullemar, V.; Melton, Phillip; Oh, S.; Yang, I.; Burrows, K.; Söderhäll, C.; Jima, D.; Gao, L.; Arathimos, R.; Küpers, L.; Wielscher, M.; Rzehak, P.; Lahti, J.; Laprise, C.; Madore, A.; Ward, J.; Bennett, B.; Wang, T.; Bell, D.; Vonk, J.; Håberg, S.; Zhao, S.; Karlsson, R.; Hollams, E.; Hu, D.; Richards, A.; Bergström, A.; Sharp, G.; Felix, J.; Bustamante, M.; Gruzieva, O.; Maguire, R.; Gilliland, F.; Baïz, N.; Nohr, E.; Corpeleijn, E.; Sebert, S.; Karmaus, W.; Grote, V.; Kajantie, E.; Magnus, M.; Örtqvist, A.; Eng, C.; Liu, A.; Kull, I.; Jaddoe, V.; Sunyer, J.; Kere, J.; Hoyo, C.; Annesi-Maesano, I. (2019)© 2018 Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to ...
Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthoodLillycrop, K.; Garratt, E.; Titcombe, P.; Melton, Phillip; Murray, R.; Barton, S.; Clarke-Harris, R.; Costello, P.; Holbrook, J.; Hopkins, J.; Childs, C.; Paras-Chavez, C.; Calder, P.; Mori, T.; Beilin, L.; Burdge, G.; Gluckman, P.; Inskip, H.; Harvey, N.; Hanson, M.; Huang, R.; Cooper, C.; Godfrey, K. (2019)© 2019, The Author(s). Background: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin ...