Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium.

Sharp, G. C.; Salas, L. A.; Monnereau, C.; Allard, C.; Yousefi, P.; Everson, T.; The Pregnancy and Childhood Epigenetics (PACE) Con,; London, S. J.; Felix, J. F.; Relton, C. L.

doi:10.1101/125492

bioRxiv · 10.1101/125492

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium.

Sharp, G. C.·Salas, L. A.·Monnereau, C.·Allard, C.·Yousefi, P.·Everson, T.·The Pregnancy and Childhood Epigenetics (PACE) Con,·London, S. J.·Felix, J. F.·Relton, C. L.

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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.\n\nWithin 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.\n\nIn 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.\n\nIn conclusion, maternal adiposity is associated with modest variations in newborn blood DNA methylation, but the potential biological consequences of these variations are currently unclear.

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Sharp, G. C., Salas, L. A., Monnereau, C., Allard, C., Yousefi, P., Everson, T., The Pregnancy and Childhood Epigenetics (PACE) Con,, London, S. J., Felix, J. F., Relton, C. L.. 2017-04-13. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium.. https://doi.org/10.1101/125492

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