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Title: | Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age | Authors: | Merid, Simon Kebede Novoloaca, Alexei Sharp, Gemma C. Kupers, Leanne K. Kho, Alvin T. Roy, Ritu Gao, Lu Annesi-Maesano, Isabella Jain, Pooja PLUSQUIN, Michelle Kogevinas, Manolis Allard, Catherine Vehmeijer, Florianne O. Kazmi, Nabila Salas, Lucas A. Rezwan, Faisal I. Zhang, Hongmei Sebert, Sylvain Czamara, Darina Rifas-Shiman, Sheryl L. Melton, Phillip E. Lawlor, Debbie A. Pershagen, Goran Breton, Carrie V. Huen, Karen Baiz, Nour Gagliardi, Luigi NAWROT, Tim Corpeleijn, Eva Perron, Patrice Duijts, Liesbeth Nohr, Ellen Aagaard Bustamante, Mariona Ewart, Susan L. Karmaus, Wilfried Zhao, Shanshan Page, Christian M. Herceg, Zdenko Jarvelin, Marjo-Riitta Lahti, Jari Baccarelli, Andrea A. Anderson, Denise Kachroo, Priyadarshini Relton, Caroline L. Bergstrom, Anna Eskenazi, Brenda Soomro, Munawar Hussain Vineis, Paolo Snieder, Harold Bouchard, Luigi Jaddoe, Vincent W. Sorensen, Thorkild I. A. Vrijheid, Martine Arshad, S. Hasan Holloway, John W. Haberg, Siri E. Magnus, Per Dwyer, Terence Binder, Elisabeth B. DeMeo, Dawn L. Vonk, Judith M. Newnham, John Tantisira, Kelan G. Kull, Inger Wiemels, Joseph L. Heude, Barbara Sunyer, Jordi Nystad, Wenche Munthe-Kaas, Monica C. Raikkonen, Katri Oken, Emily Huang, Rae-Chi Weiss, Scott T. Anto, Josep Maria Bousquet, Jean Kumar, Ashish Soderhall, Cilla Almqvist, Catarina Cardenas, Andres Gruzieva, Olena Xu, Cheng-Jian Reese, Sarah E. Kere, Juha Brodin, Petter Solomon, Olivia Wielscher, Matthias Holland, Nina Ghantous, Akram Hivert, Marie-France Felix, Janine F. Koppelman, Gerard H. London, Stephanie J. Melen, Erik |
Issue Date: | 2020 | Publisher: | BMC | Source: | Genome Medicine, 12 (1) (Art N° 25) | 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 < 1.06 x 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. | Notes: | Melen, E (reprint author), Karolinska Inst, Inst Environm Med, Stockholm, Sweden.; Melen, E (reprint author), Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden. erik.melen@ki.se |
Other: | Melen, E (reprint author), Karolinska Inst, Inst Environm Med, Stockholm, Sweden; Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden. erik.melen@ki.se | Keywords: | Development;Epigenetics;Gestational age;Preterm birth;Transcriptomics | Document URI: | http://hdl.handle.net/1942/30893 | ISSN: | 1756-994X | e-ISSN: | 1756-994X | DOI: | 10.1186/s13073-020-0716-9 | ISI #: | WOS:000517604800001 | Rights: | The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2021 |
Appears in Collections: | Research publications |
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