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A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health.


ABSTRACT: Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.

SUBMITTER: Fernandez-Jimenez N 

PROVIDER: S-EPMC9709064 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health.

Fernandez-Jimenez Nora N   Fore Ruby R   Cilleros-Portet Ariadna A   Lepeule Johanna J   Perron Patrice P   Kvist Tuomas T   Tian Fu-Ying FY   Lesseur Corina C   Binder Alexandra M AM   Lozano Manuel M   Martorell-Marugán Jordi J   Loke Yuk J YJ   Bakulski Kelly M KM   Zhu Yihui Y   Forhan Anne A   Sammallahti Sara S   Everson Todd M TM   Chen Jia J   Michels Karin B KB   Belmonte Thalia T   Carmona-Sáez Pedro P   Halliday Jane J   Daniele Fallin M M   LaSalle Janine M JM   Tost Jorg J   Czamara Darina D   Fernández Mariana F MF   Gómez-Martín Antonio A   Craig Jeffrey M JM   Gonzalez-Alzaga Beatriz B   Schmidt Rebecca J RJ   Dou John F JF   Muggli Evelyne E   Lacasaña Marina M   Vrijheid Martine M   Marsit Carmen J CJ   Karagas Margaret R MR   Räikkönen Katri K   Bouchard Luigi L   Heude Barbara B   Santa-Marina Loreto L   Bustamante Mariona M   Hivert Marie-France MF   Bilbao Jose Ramon JR  

Communications biology 20221130 1


Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from t  ...[more]

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