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Cited by 20Birth, Development, and HealthEpigenetics and DNA MethylationGestational Diabetes Research and Management

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

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Fernandez-Jimenez, Nora, Fore, Ruby, Cilleros-Portet, Ariadna, Lepeule, Johanna, Perron, Patrice, Kvist, Tuomas, Tian, Fu-Ying, Lesseur, Corina +36 more·2022·Communications Biology
DOI 10.1038/s42003-022-04267-yPMC PMC9709064
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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.

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  • A meta-analysis of 10 cohorts comprising 2631 mother-infant pairs identified 27 placental CpG sites associated with maternal prepregnancy BMI, with DNA methylation differences of up to 2.0% per 10-unit increase in prepregnancy BMI.

    “A meta-analysis of 10 cohorts comprising 2631 mother–infant pairs identified 27 placental CpG sites associated with maternal prepregnancy body mass index (BMI), with DNA methylation differences of up to 2.0% per 10-unit increase in prepregnancy BMI [30].”

    From Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures (2026) · cites this paper as [30]

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References 66 · Cited by 20

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Authors
Fernandez-Jimenez, N., Fore, R., Cilleros-Portet, A., Lepeule, J., Perron, P., Kvist, T., Tian, F.-Y., Lesseur, C., Binder, A. M., Lozano, M., Martorell-Marugán, J., Loke, Y. J., Bakulski, K. M., Zhu, Y., Forhan, A., Sammallahti, S., Everson, T. M., Chen, J., Michels, K. B., Belmonte, T., Carmona-Sáez, P., Halliday, J., Daniele Fallin, M., LaSalle, J. M., Tost, J., Czamara, D., Fernández, M. F., Gómez-Martín, A., Craig, J. M., Gonzalez-Alzaga, B., Schmidt, R. J., Dou, J. F., Muggli, E., Lacasaña, M., Vrijheid, M., Marsit, C. J., Karagas, M. R., Räikkönen, K., Bouchard, L., Heude, B., Santa-Marina, L., Bustamante, M., Hivert, M.-F., & Bilbao, J. R.
Affiliations
  • Harvard University (US)
  • Centre National de la Recherche Scientifique (FR)
  • Centre de recherche du CHUS (CA)
  • University of Helsinki (FI)
  • Emory University (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • University of California, Los Angeles (US)
  • Universitat Jaume I (ES)
  • The University of Melbourne (AU)
  • University of Michigan (US)
  • University of California, Davis (US)
  • Inserm (FR)
  • Erasmus MC (NL)
  • University of Freiburg (DE)
  • Max Planck Institute of Psychiatry (DE)
  • Universidad de Granada (ES)
  • Deakin University (AU)
  • Instituto de Investigación Biosanitaria de Granada (ES)
  • Universitat Pompeu Fabra (ES)
  • Université de Sherbrooke (CA)
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2022-11-30
Volume
5
Issue
1
Pages
1313-1313
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-022-04267-y
PMC
PMC9709064
OpenAlex
W4310368196
Cited by
20
References
66
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 2 · 2022: 1
FWCI
1.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
  • RODIN (Universidad de Cádiz) (publishedVersion, cc-by)
  • HAL (submittedVersion, other-oa)
  • eScholarship (California Digital Library) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, cc-by-nc)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
  • Communities in ADDI (University of the Basque Country) (submittedVersion, cc-by)
  • Institutional Repository of the University of Granada (University of Granada) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • Hispana (submittedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
Funders
  • Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (PI18/01142)
  • Osasun Saila, Eusko Jaurlaritzako (GVSAN2018111086)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Keywords
pre-pregnancy body mass index, maternal obesity, placental DNA methylation, epigenome-wide association study, CpG sites, maternal and child health, neonatal morbidity, pregnancy complications, offspring metabolic outcomes, glutathione peroxidase 1, LGR4, oxidative stress, cancer pathways
MeSH terms
Child Health, Child, Female, Humans, Infant, Newborn, Mothers, Placenta, Pregnancy, Body Mass Index, DNA Methylation

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