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Title: | Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude | Authors: | Kadalayil, Latha Alam, Md. Zahangir White, Cory Haley Ghantous, Akram Walton, Esther Gruzieva, Olena Merid, Simon Kebede Kumar, Ashish Roy, Ritu P. Solomon, Olivia Huen, Karen Eskenazi, Brenda Rzehak, Peter Grote, Veit Langhendries, Jean-Paul Verduci, Elvira Ferre, Natalia Gruszfeld, Darek Gao, Lu Guan, Weihua Zeng, Xuehuo Schisterman, Enrique F. Dou, John F. Bakulski, Kelly M. Feinberg, Jason I. Soomro, Munawar Hussain Pesce, Giancarlo Baiz, Nour Isaevska, Elena PLUSQUIN, Michelle Vafeiadi, Marina Roumeliotaki, Theano LANGIE, Sabine Standaert, Arnout Allard, Catherine Perron, Patrice Bouchard, Luigi van Meel, Evelien R. Felix, Janine F. Jaddoe, Vincent W. V. Yousefi, Paul D. Ramlau-Hansen, Cecilia H. Relton, Caroline L. Tobi, Elmar W. Starling, Anne P. Yang, Ivana V. Llambrich, Maria Santorelli, Gillian Lepeule, Johanna Salas, Lucas A. Bustamante, Mariona Ewart, Susan L. Zhang , Hongmei Karmaus, Wilfried Roeder, Stefan Zenclussen, Ana Claudia Jin, Jianping Nystad, Wenche Page, Christian M. Magnus, Maria Jima, Dereje D. Hoyo, Cathrine Maguire, Rachel L. Kvist, Tuomas Czamara, Darina Raikkonen, Katri Gong, Tong Ullemar, Vilhelmina Rifas-Shiman, Sheryl L. Oken, Emily Almqvist, Catarina Karlsson, Robert Lahti, Jari Murphy, Susan K. Haberg, Siri E. London, Stephanie Herberth, Gunda Arshad, Hasan Sunyer, Jordi Grazuleviciene, Regina Dabelea, Dana Steegers-Theunissen, Regine P. M. Nohr, Ellen A. Sorensen, Thorkild I. A. Duijts, Liesbeth Hivert, Marie-France Nelen, Vera Popovic, Maja Kogevinas, Manolis NAWROT, Tim Herceg, Zdenko Annesi-Maesano, Isabella Fallin, M. Daniele Yeung, Edwina Breton, Carrie V. Koletzko, Berthold Holland, Nina Wiemels, Joseph L. Melen, Erik Sharp, Gemma C. Silver, Matt J. Rezwan, Faisal, I Holloway, John W. |
Issue Date: | 2023 | Publisher: | BMC | Source: | Clinical Epigenetics, 15 (1) (Art N° 148) | Abstract: | Background Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. Methods We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. Results We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (>= 50 degrees N), lower (< 50 degrees N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (>= 50 degrees N). Conclusions In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes. | Notes: | Holloway, JW (corresponding author), Univ Southampton, Southampton Gen Hosp, Human Dev & Hlth, Fac Med, Southampton, Hants, England.; Holloway, JW (corresponding author), Southampton Gen Hosp, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England. J.W.Holloway@soton.ac.uk |
Keywords: | PACE;Meta-analysis;Birth season;DNA methylation;Differentially methylated regions (DMR);Latitude | Document URI: | http://hdl.handle.net/1942/41743 | ISSN: | 1868-7075 | e-ISSN: | 1868-7083 | DOI: | 10.1186/s13148-023-01542-5 | ISI #: | 001068850100001 | Rights: | The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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