A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health
Nora Fernandez-Jimenez
(1, 2)
,
Ruby Fore
(3)
,
Ariadna Cilleros-Portet
(1, 2)
,
Johanna Lepeule
(4)
,
Patrice Perron
(5)
,
Tuomas Kvist
(6)
,
Fu-Ying Tian
(7)
,
Corina Lesseur
(8)
,
Alexandra M. Binder
(9, 10)
,
Manuel Lozano
(11, 12)
,
Jordi Martorell-Marugan
(13)
,
Yuk J. Loke
(14, 15)
,
Kelly M. Bakulski
(16)
,
Yihui Zhu
(17)
,
Anne Forhan
(18)
,
Sara Sammallahti
(19)
,
Todd M. Everson
(7)
,
Jia Chen
(8)
,
Karin B. Michels
(10, 20)
,
Thalia Belmonte
(21)
,
Pedro Carmona-Saez
(13)
,
Jane Halliday
(14, 22)
,
M. Daniele Fallin
(23)
,
Janine M. Lasalle
(24)
,
Jorg Tost
(25)
,
Darina Czamara
(26)
,
Mariana F. Fernandez
(13, 27)
,
Antonio Gomez-Martin
(28)
,
Jeffrey M. Craig
(14, 29)
,
Beatriz Gonzalez-Alzaga
(28)
,
Rebecca J. Schmidt
(17)
,
John F. Dou
(16)
,
Evelyne Muggli
(14, 22)
,
Marina Lacasaña
(28, 27)
,
Martine Vrijheid
(27, 30, 31)
,
Carmen J. Marsit
(7)
,
Margaret R. Karagas
(32)
,
Katri Raikkonen
(6)
,
Luigi Bouchard
(32)
,
Barbara Heude
(18)
,
Loreto Santa-Marina
(27)
,
Mariona Bustamante
(27, 30, 31)
,
Marie-France Hivert
(3, 5, 33)
,
Jose Ramon Bilbao
(1, 34)
1
UPV / EHU -
University of the Basque Country = Euskal Herriko Unibertsitatea
2 Biocruces Bizkaia Health Research Institute [Baracaldo]
3 HMS - Harvard Medical School [Boston]
4 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
5 UdeS - Université de Sherbrooke
6 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
7 Emory University [Atlanta, GA]
8 MSSM - Icahn School of Medicine at Mount Sinai [New York]
9 UH - University of Hawai'i [Honolulu]
10 Fielding School of Public Health
11 FISABIO - Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne]
12 UV - Universitat de València
13 UGR - Universidad de Granada = University of Granada
14 MCRI - Murdoch Children's Research Institute
15 University of Melbourne
16 University of Michigan [Ann Arbor]
17 UC Davis - University of California [Davis]
18 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
19 Erasmus MC - Erasmus University Medical Center [Rotterdam]
20 Faculty of Medicine and Medical Center
21 Puerta del Mar University Hospital
22 Department of Paediatrics [Melbourne]
23 Johns Hopkins Bloomberg School of Public Health [Baltimore]
24 Genome Center [UC Davis]
25 LEE - Laboratoire Epigénétique et environnement
26 Max Planck Institute of Psychiatry
27 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
28 Andalusian School of Public Health [Granada]
29 Deakin University [Burwood]
30 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
31 UPF - Universitat Pompeu Fabra [Barcelona]
32 Department of Biochemistry and Functional Genomics
33 Massachusetts General Hospital [Boston]
34 CIBERDEM - Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas
2 Biocruces Bizkaia Health Research Institute [Baracaldo]
3 HMS - Harvard Medical School [Boston]
4 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
5 UdeS - Université de Sherbrooke
6 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
7 Emory University [Atlanta, GA]
8 MSSM - Icahn School of Medicine at Mount Sinai [New York]
9 UH - University of Hawai'i [Honolulu]
10 Fielding School of Public Health
11 FISABIO - Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne]
12 UV - Universitat de València
13 UGR - Universidad de Granada = University of Granada
14 MCRI - Murdoch Children's Research Institute
15 University of Melbourne
16 University of Michigan [Ann Arbor]
17 UC Davis - University of California [Davis]
18 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
19 Erasmus MC - Erasmus University Medical Center [Rotterdam]
20 Faculty of Medicine and Medical Center
21 Puerta del Mar University Hospital
22 Department of Paediatrics [Melbourne]
23 Johns Hopkins Bloomberg School of Public Health [Baltimore]
24 Genome Center [UC Davis]
25 LEE - Laboratoire Epigénétique et environnement
26 Max Planck Institute of Psychiatry
27 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
28 Andalusian School of Public Health [Granada]
29 Deakin University [Burwood]
30 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
31 UPF - Universitat Pompeu Fabra [Barcelona]
32 Department of Biochemistry and Functional Genomics
33 Massachusetts General Hospital [Boston]
34 CIBERDEM - Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas
Résumé
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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