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Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude

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dc.contributor.author Kadalayil, Latha
dc.contributor.author Llambrich, Maria
dc.contributor.author Salas Díaz, Lucas Andrés, 1980-
dc.contributor.author Bustamante Pineda, Mariona
dc.contributor.author Sunyer Deu, Jordi
dc.contributor.author Kogevinas, Manolis
dc.contributor.author Holloway, John W.
dc.date.accessioned 2023-12-11T06:37:05Z
dc.date.available 2023-12-11T06:37:05Z
dc.date.issued 2023
dc.identifier.citation Kadalayil L, Alam MZ, White CH, Ghantous A, Walton E, Gruzieva O, et al. Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude. Clin Epigenetics. 2023 Sep 11;15(1):148. DOI: 10.1186/s13148-023-01542-5
dc.identifier.issn 1868-7075
dc.identifier.uri http://hdl.handle.net/10230/58463
dc.description.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°N), lower (< 50°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°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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof Clin Epigenetics. 2023 Sep 11;15(1):148
dc.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://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s13148-023-01542-5
dc.subject.keyword Birth season
dc.subject.keyword DNA methylation
dc.subject.keyword Differentially methylated regions (DMR)
dc.subject.keyword Latitude
dc.subject.keyword Meta-analysis
dc.subject.keyword PACE
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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