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

Merid, Simon Kebede and Novoloaca, Alexei and Sharp, Gemma C. and Küpers, Leanne K. and Kho, Alvin T. and Roy, Ritu and Gao, Lu and Annesi-Maesano, Isabella and Jain, Pooja and Plusquin, Michelle and Kogevinas, Manolis and Allard, Catherine and Vehmeijer, Florianne O. and Kazmi, Nabila and Salas, Lucas A. and Rezwan, Faisal I. and Zhang, Hongmei and Sebert, Sylvain and Czamara, Darina and Rifas-Shiman, Sheryl L. and Melton, Phillip E. and Lawlor, Debbie A. and Pershagen, Göran and Breton, Carrie V. and Huen, Karen and Baiz, Nour and Gagliardi, Luigi and Nawrot, Tim S. and Corpeleijn, Eva and Perron, Patrice and Duijts, Liesbeth and Nohr, Ellen Aagaard and Bustamante, Mariona and Ewart, Susan L. and Karmaus, Wilfried and Zhao, Shanshan and Page, Christian M. and Herceg, Zdenko and Jarvelin, Marjo-Riitta and Lahti, Jari and Baccarelli, Andrea A. and Anderson, Denise and Kachroo, Priyadarshini and Relton, Caroline L. and Bergström, Anna and Eskenazi, Brenda and Soomro, Munawar Hussain and Vineis, Paolo and Snieder, Harold and Bouchard, Luigi and Jaddoe, Vincent W. and Sørensen, Thorkild I. A. and Vrijheid, Martine and Arshad, S. Hasan and Holloway, John W. and Håberg, Siri E. and Magnus, Per and Dwyer, Terence and Binder, Elisabeth B. and DeMeo, Dawn L. and Vonk, Judith M. and Newnham, John and Tantisira, Kelan G. and Kull, Inger and Wiemels, Joseph L. and Heude, Barbara and Sunyer, Jordi and Nystad, Wenche and Munthe-Kaas, Monica C. and Räikkönen, Katri and Oken, Emily and Huang, Rae-Chi and Weiss, Scott T. and Antó, Josep Maria and Bousquet, Jean and Kumar, Ashish and Söderhäll, Cilla and Almqvist, Catarina and Cardenas, Andres and Gruzieva, Olena and Xu, Cheng-Jian and Reese, Sarah E. and Kere, Juha and Brodin, Petter and Solomon, Olivia and Wielscher, Matthias and Holland, Nina and Ghantous, Akram and Hivert, Marie-France and Felix, Janine F. and Koppelman, Gerard H. and London, Stephanie J. and Melén, Erik. (2020) Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age. Genome medicine, 12. p. 25.

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Abstract

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.; 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.; 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.; 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Swiss Centre for International Health (SCIH) > Digital Health Unit (Raab)
UniBasel Contributors:Kumar, Ashish
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:BioMed Central
ISSN:1756-994X
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
edoc DOI:
Last Modified:27 Mar 2020 07:15
Deposited On:27 Mar 2020 07:15

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