Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Todd M. Everson, et al.

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Received Date: 20th May 19

Todd M. Everson, Marta Vives-Usano, Emie Seyve, Andres Cardenas, Marina Lacasaña, Jeffrey M. Craig, Corina Lesseur, Emily R. Baker, Nora Fernandez-Jimenez, Barbara Heude, Patrice Perron, Beatriz Gónzalez-Alzaga, Jane Halliday, Maya A. Deyssenroth, Margaret R. Karagas, Carmen Íñiguez, Luigi Bouchard, Pedro Carmona-Sáez, Yuk J. Loke, Ke Hao, Thalia Belmonte, Marie A. Charles, Jordi Martorell-Marugán, Evelyne Muggli, Jia Chen, Mariana F. Fernández, Jorg Tost, Antonio Gómez-Martín, Stephanie J. London, Jordi Sunyer, Carmen J. Marsit, Johanna Lepeule, Marie-France Hivert, Mariona Bustamante

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature