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

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Merid, SK, Novoloaca, A, Sharp, GC, Kupers, LK, Kho, AT, Roy, R, Gao, L, Annesi-Maesano, I, Jain, P, Plusquin, M, Kogevinas, M, Allard, C, Vehmeijer, FO, Kazmi, N, Salas, LA, Rezwan, FI, Zhang, H, Sebert, S, Czamara, D, Rifas-Shiman, SL, Melton, PE ORCID: 0000-0003-4026-2964, Lawlor, DA, Pershagen, G, Breton, CV, Huen, K, Baiz, N, Gagliardi, L, Nawrot, TS, Corpeleijn, E, Perron, P, Duijts, L, Nohr, EA, Bustamante, M, Ewart, SL, Karmaus, W, Zhao, S, Page, CM, Herceg, Z, Jarvelin, M-R, Lahti, J, Baccarelli, AA, Anderson, D, Kachroo, P, Relton, CL, Bergstrom, A, Eskenazi, B, Soomro, MH, Vineis, P, Snieder, H, Bouchard, L, Jaddoe, VW, Sorensen, TIA, Vrijheid, M, Arshad, SH, Holloway, JW, Haberg, SE, Magnus, P, Dwyer, T, Binder, EB, Demeo, DL, Vonk, JM, Newnham, J, Tantisira, KG, Kull, I, Wiemels, JL, Heude, B, Sunyer, J, Nystad, W, Munthe-Kaas, MC, Raikkonen, K, Oken, E, Huang, R-C, Weiss, ST, Anto, JM, Bousquet, J, Kumar, A, Soderhall, C, Almqvist, C, Cardenas, A, Gruzieva, O, Xu, C-J, Reese, SE, Kere, J, Brodin, P, Solomon, O, Wielscher, M, Holland, N, Ghantous, A, Hivert, M-F, Felix, JF, Koppelman, GH, London, SJ and Melen, E 2020 , 'Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age' , Genome Medicine, vol. 12, no. 1 , pp. 1-17 , doi: 10.1186/s13073-020-0716-9.

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Abstract

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 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.

Item Type: Article
Authors/Creators:Merid, SK and Novoloaca, A and Sharp, GC and Kupers, LK and Kho, AT and Roy, R and Gao, L and Annesi-Maesano, I and Jain, P and Plusquin, M and Kogevinas, M and Allard, C and Vehmeijer, FO and Kazmi, N and Salas, LA and Rezwan, FI and Zhang, H and Sebert, S and Czamara, D and Rifas-Shiman, SL and Melton, PE and Lawlor, DA and Pershagen, G and Breton, CV and Huen, K and Baiz, N and Gagliardi, L and Nawrot, TS and Corpeleijn, E and Perron, P and Duijts, L and Nohr, EA and Bustamante, M and Ewart, SL and Karmaus, W and Zhao, S and Page, CM and Herceg, Z and Jarvelin, M-R and Lahti, J and Baccarelli, AA and Anderson, D and Kachroo, P and Relton, CL and Bergstrom, A and Eskenazi, B and Soomro, MH and Vineis, P and Snieder, H and Bouchard, L and Jaddoe, VW and Sorensen, TIA and Vrijheid, M and Arshad, SH and Holloway, JW and Haberg, SE and Magnus, P and Dwyer, T and Binder, EB and Demeo, DL and Vonk, JM and Newnham, J and Tantisira, KG and Kull, I and Wiemels, JL and Heude, B and Sunyer, J and Nystad, W and Munthe-Kaas, MC and Raikkonen, K and Oken, E and Huang, R-C and Weiss, ST and Anto, JM and Bousquet, J and Kumar, A and Soderhall, C and Almqvist, C and Cardenas, A and Gruzieva, O and Xu, C-J and Reese, SE and Kere, J and Brodin, P and Solomon, O and Wielscher, M and Holland, N and Ghantous, A and Hivert, M-F and Felix, JF and Koppelman, GH and London, SJ and Melen, E
Keywords: development, epigenetics, gestational age, preterm birth, transcriptomics
Journal or Publication Title: Genome Medicine
Publisher: BioMed Central Ltd.
ISSN: 1756-994X
DOI / ID Number: 10.1186/s13073-020-0716-9
Copyright Information:

Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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