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Article Dans Une Revue Genome Medicine Année : 2020

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Simon Kebede Merid (1, 2) , Alexei Novoloaca (3) , Gemma C Sharp (4, 5) , Leanne K Küpers (5, 6, 7) , Alvin T Kho (8) , Ritu Roy (9, 10) , Lu Gao (11) , Isabella Annesi-Maesano (12, 13) , Pooja Jain (14, 15) , Michelle Plusquin (14, 16) , Manolis Kogevinas (17, 18, 19, 20) , Catherine Allard (21) , Florianne O Vehmeijer (22) , Nabila Kazmi (4, 5) , Lucas A Salas (23) , Faisal I Rezwan (24) , Hongmei Zhang (25) , Sylvain Sebert (26, 27, 15) , Darina Czamara (28) , Sheryl L Rifas-Shiman (29, 30) , Phillip E Melton (31, 32) , Debbie A Lawlor (4, 5, 33) , Göran Pershagen (1, 34) , Carrie V Breton (35) , Karen Huen (36) , Nour Baiz (13, 12) , Luigi Gagliardi (37) , Tim S Nawrot (38, 39) , Eva Corpeleijn (40) , Patrice Perron (41) , Liesbeth Duijts (22) , Ellen Aagaard Nohr (42) , Mariona Bustamante (17, 18, 19) , Susan L Ewart (43) , Wilfried Karmaus (25) , Shanshan Zhao (44) , Christian M Page (45) , Zdenko Herceg (46) , Marjo-Riitta Jarvelin (26, 27, 47) , Jari Lahti (48, 49) , Andrea A Baccarelli (50) , Denise Anderson (51) , Priyadarshini Kachroo (52) , Caroline L Relton (4, 5, 33) , Anna Bergström (1, 34) , Brenda Eskenazi (36) , Munawar Hussain Soomro (12, 13) , Paolo Vineis (15) , Harold Snieder (40) , Luigi Bouchard (21, 53) , Vincent W Jaddoe (22) , Thorkild I A Sørensen (4, 54, 55) , Martine Vrijheid (17, 18, 19) , S Hasan Arshad (56, 57) , John W Holloway (58) , Siri E Håberg (45) , Per Magnus (45) , Terence Dwyer (59, 60) , Elisabeth B Binder (28, 61) , Dawn L Demeo (62) , Judith M Vonk (40, 63) , John Newnham (32) , Kelan G Tantisira (62) , Inger Kull (64, 65) , Joseph L Wiemels (35) , Barbara Heude (66, 67) , Jordi Sunyer (17, 18, 19, 20) , Wenche Nystad (45) , Monica C Munthe-Kaas (45, 68) , Katri Räikkönen (45) , Emily Oken (29, 30) , Rae-Chi Huang (51) , Scott T Weiss (69) , Josep Maria Antó (17, 18, 19, 20) , Jean Bousquet (70, 71) , Ashish Kumar (1, 72, 73) , Cilla Söderhäll (1) , Catarina Almqvist (1, 74) , Andres Cardenas (75) , Olena Gruzieva (1, 34) , Cheng-Jian Xu (40, 76, 63) , Sarah E Reese (44) , Juha Kere (1, 77) , Petter Brodin (1, 78, 79) , Olivia Solomon (36) , Matthias Wielscher (47) , Nina Holland (36) , Akram Ghantous (46) , Marie-France Hivert (41, 29, 30, 80) , Janine F Felix (22) , Gerard H Koppelman (40, 76, 63) , Stephanie J London (44) , Erik Melén (1, 65)
1 Karolinska Institutet [Stockholm]
2 Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm
3 IACR - International Agency for Cancer Research
4 MRC IEU - MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni]
5 Bristol Medical School
6 WUR - Wageningen University and Research [Wageningen]
7 University of Groningen [Groningen]
8 Boston Children's Hospital
9 UC San Francisco - University of California [San Francisco]
10 Helen Diller Family Comprehensive Cancer Center [San Francisco]
11 SCU - Southern California University of Health Sciences
12 EPAR - Epidemiology of Allergic and Respiratory Diseases Department [iPlesp]
13 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
14 NIHR Biomedical Research Centre [London]
15 Imperial College London
16 UHasselt - Hasselt University
17 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
18 UPF - Universitat Pompeu Fabra [Barcelona]
19 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
20 IMIM-Hospital del Mar
21 UdeS - Faculté de médecine et des sciences de la santé [Sherbrooke]
22 Erasmus MC - Erasmus University Medical Center [Rotterdam]
23 Geisel School of Medicine at Dartmouth
24 Cranfield University
25 U of M - University of Memphis
26 University of Oulu
27 Department of Biology and Biocenter Oulu
28 Max Planck Institute of Psychiatry
29 HMS - Harvard Medical School [Boston]
30 Harvard Pilgrim Health Care Institute
31 Curtin University
32 UWA - The University of Western Australia
33 NIHR Bristol Biomedical Research Centre
34 Region Stockholm - Centre for Occupational and Environmental Medicine [Stockholm, Sweden]
35 USC - University of Southern California
36 UC Berkeley - University of California [Berkeley]
37 USL Tuscany Northwest
38 NIHR Health Protection Research Unit
39 University Hospitals Leuven [Leuven]
40 UMCG - University Medical Center Groningen [Groningen]
41 CHUS – Centre Hospitalier Universitaire de Sherbrooke [Sherbrooke, QC, Canada]
42 SDU - University of Southern Denmark
43 Michigan State University [East Lansing]
44 NIEHS-NIH - National Institute of Environmental Health Sciences [Durham, NC, USA]
45 NIPH - Norwegian Institute of Public Health [Oslo]
46 CIRC - IARC - Centre International de Recherche contre le Cancer - International Agency for Research on Cancer
47 MRC-PHE Centre for Environment and Health
48 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
49 Turku Institute for Advanced Studies
50 Columbia Mailman School of Public Health
51 Telethon KIDS Institute
52 Brigham and Women’s Hospital [Boston, MA]
53 Département des Sciences Fondamentales [Saguenay, QC, Canada]
54 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
55 UCPH - University of Copenhagen = Københavns Universitet
56 University of Southampton
57 The David Hide Asthma and Allergy Research Centre
58 University Hospital Southampton NHS Foundation Trust
59 NDWRH - Nuffield Department of Women's and Reproductive Health
60 MCRI - Murdoch Children's Research Institute
61 Emory University School of Medicine
62 Brigham and Women's Hospital [Boston]
63 Groningen Research Institute for Asthma and COPD (GRIAC)
64 Karolinska Institutet Science Park
65 Sachs' Children's Hospital
66 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
67 EarOH - Research Team on Early life Origins of Health
68 Oslo University Hospital [Oslo]
69 BWH - Brigham & Women’s Hospital [Boston]
70 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
71 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
72 Unibas - Université de Bâle = University of Basel = Basel Universität
73 Swiss Tropical and Public Health Institute [Basel]
74 Astrid Lindgren Children's Hospital
75 School of Public Health [Berkeley]
76 Beatrix Children's Hospital
77 Folkhälsan Research Center
78 Karolinska University Hospital [Stockholm]
79 Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17165 Sweden.
80 Massachusetts General Hospital [Boston]
Darina Czamara
Rae-Chi Huang
Andres Cardenas

Résumé

Background. Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results. We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P< 1.06 × 10 − 7 , of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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hal-03537765 , version 1 (20-01-2022)

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Simon Kebede Merid, Alexei Novoloaca, Gemma C Sharp, Leanne K Küpers, Alvin T Kho, et al.. Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age. Genome Medicine, 2020, 12 (1), pp.25. ⟨10.1186/s13073-020-0716-9⟩. ⟨hal-03537765⟩
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