TY - JOUR
T1 - A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health
AU - Fernandez-Jimenez, Nora
AU - Fore, Ruby
AU - Cilleros-Portet, Ariadna
AU - Lepeule, Johanna
AU - Perron, Patrice
AU - Kvist, Tuomas
AU - Tian, Fu Ying
AU - Lesseur, Corina
AU - Binder, Alexandra M.
AU - Lozano, Manuel
AU - Martorell-Marugán, Jordi
AU - Loke, Yuk J.
AU - Bakulski, Kelly M.
AU - Zhu, Yihui
AU - Forhan, Anne
AU - Sammallahti, Sara
AU - Everson, Todd M.
AU - Chen, Jia
AU - Michels, Karin B.
AU - Belmonte, Thalia
AU - Carmona-Sáez, Pedro
AU - Halliday, Jane
AU - Daniele Fallin, M.
AU - LaSalle, Janine M.
AU - Tost, Jorg
AU - Czamara, Darina
AU - Fernández, Mariana F.
AU - Gómez-Martín, Antonio
AU - Craig, Jeffrey M.
AU - Gonzalez-Alzaga, Beatriz
AU - Schmidt, Rebecca J.
AU - Dou, John F.
AU - Muggli, Evelyne
AU - Lacasaña, Marina
AU - Vrijheid, Martine
AU - Marsit, Carmen J.
AU - Karagas, Margaret R.
AU - Räikkönen, Katri
AU - Bouchard, Luigi
AU - Heude, Barbara
AU - Santa-Marina, Loreto
AU - Bustamante, Mariona
AU - Hivert, Marie France
AU - Bilbao, Jose Ramon
N1 - Funding Information:
We would like to thank the Pregnancy and Childhood Epigenetics (PACE) consortium, as well as all the families that participated in these studies for their generous contribution. This work was partially funded by GVSAN2018111086 from the Basque Department of Health and PI18/01142 from ISCIII - Spanish Ministry of Science and Innovation - cofounded by the ERDF “A way to make Europe” to JRB and LSM, respectively; and by the Joint Programming Initiative – A Healthy Diet for a Healthy Life (JPI HDHL) (NutriPROGRAM). ACP was supported by grant GVSAN2019111085 from the Basque Department of Health to NFJ. Detailed acknowledgements and funding for each participating cohort are described in Supplementary Note .
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85142916959&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-04267-y
DO - 10.1038/s42003-022-04267-y
M3 - Article
C2 - 36446949
AN - SCOPUS:85142916959
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 1313
ER -