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

Todd M. Everson; Marta Vives-Usano; Emie Seyve; Andrés Cárdenas; Marina Lacasaña; Jeffrey Mark Craig; Corina Lesseur; Emily Baker; Nora Fernández‐Jiménez; Barbara Heude; Patrice Perron; Beatriz González-Alzaga; Jane L. Halliday; Maya A. Deyssenroth; Margaret Rita Karagas; Carmen Íñiguez; Luigi Bouchard; Pedro Carmona‐Sáez; Yuk Jing Loke; Ke Hao; Thalía Belmonte; Marie-Aline A Charles; Jordi Martorell‐Marugán; Evelyne Muggli; Jia Chen; Mariana Fátima Fernández; Jörg Tost; Antonio Gómez‐Martín; Stephanie J. London; Jordi Sunyer

doi:10.1038/s41467-021-24558-y

GenomicsNature CommunicationsAug 24, 2021

Peer-reviewed journal article

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

Todd M. Everson iD, Marta Vives-Usano iD, Emie Seyve, Andrés Cárdenas iD, Marina Lacasaña iD, Jeffrey Mark Craig iD, Corina Lesseur iD, Emily Baker iD, Nora Fernández‐Jiménez iD, Barbara Heude iD, Patrice Perron iD, Beatriz González-Alzaga iD, Jane L. Halliday iD, Maya A. Deyssenroth iD, Margaret Rita Karagas iD, Carmen Íñiguez iD, Luigi Bouchard iD, Pedro Carmona‐Sáez iD, Yuk Jing Loke iD, Ke Hao iD, Thalía Belmonte iD, Marie-Aline A Charles iD, Jordi Martorell‐Marugán iD, Evelyne Muggli iD, Jia Chen iD, , Mariona Bustamante iD

Abstract

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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