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dc.contributor.authorKadalayil, L
dc.contributor.authorAlam, MZ
dc.contributor.authorWhite, CH
dc.contributor.authorGhantous, A
dc.contributor.authorWalton, E
dc.contributor.authorGruzieva, O
dc.contributor.authorMerid, SK
dc.contributor.authorKumar, A
dc.contributor.authorRoy, RP
dc.contributor.authorSolomon, O
dc.contributor.authorHuen, K
dc.contributor.authorEskenazi, B
dc.contributor.authorRzehak, P
dc.contributor.authorGrote, V
dc.contributor.authorLanghendries, J-P
dc.contributor.authorVerduci, E
dc.contributor.authorFerre, N
dc.contributor.authorGruszfeld, D
dc.contributor.authorGao, L
dc.contributor.authorGuan, W
dc.contributor.authorZeng, X
dc.contributor.authorSchisterman, EF
dc.contributor.authorDou, JF
dc.contributor.authorBakulski, KM
dc.contributor.authorFeinberg, JI
dc.contributor.authorSoomro, MH
dc.contributor.authorPesce, G
dc.contributor.authorBaiz, N
dc.contributor.authorIsaevska, E
dc.contributor.authorPlusquin, M
dc.contributor.authorVafeiadi, M
dc.contributor.authorRoumeliotaki, T
dc.contributor.authorLangie, SAS
dc.contributor.authorStandaert, A
dc.contributor.authorAllard, C
dc.contributor.authorPerron, P
dc.contributor.authorBouchard, L
dc.contributor.authorvan Meel, ER
dc.contributor.authorFelix, JF
dc.contributor.authorJaddoe, VWV
dc.contributor.authorYousefi, PD
dc.contributor.authorRamlau-Hansen, CH
dc.contributor.authorRelton, CL
dc.contributor.authorTobi, EW
dc.contributor.authorStarling, AP
dc.contributor.authorYang, IV
dc.contributor.authorLlambrich, M
dc.contributor.authorSantorelli, G
dc.contributor.authorLepeule, J
dc.contributor.authorSalas, LA
dc.contributor.authorBustamante, M
dc.contributor.authorEwart, SL
dc.contributor.authorZhang, H
dc.contributor.authorKarmaus, W
dc.contributor.authorRöder, S
dc.contributor.authorZenclussen, AC
dc.contributor.authorJin, J
dc.contributor.authorNystad, W
dc.contributor.authorPage, CM
dc.contributor.authorMagnus, M
dc.contributor.authorJima, DD
dc.contributor.authorHoyo, C
dc.contributor.authorMaguire, RL
dc.contributor.authorKvist, T
dc.contributor.authorCzamara, D
dc.contributor.authorRäikkönen, K
dc.contributor.authorGong, T
dc.contributor.authorUllemar, V
dc.contributor.authorRifas-Shiman, SL
dc.contributor.authorOken, E
dc.contributor.authorAlmqvist, C
dc.contributor.authorKarlsson, R
dc.contributor.authorLahti, J
dc.contributor.authorMurphy, SK
dc.contributor.authorHåberg, SE
dc.contributor.authorLondon, S
dc.contributor.authorHerberth, G
dc.contributor.authorArshad, H
dc.contributor.authorSunyer, J
dc.contributor.authorGrazuleviciene, R
dc.contributor.authorDabelea, D
dc.contributor.authorSteegers-Theunissen, RPM
dc.contributor.authorNohr, EA
dc.contributor.authorSørensen, TIA
dc.contributor.authorDuijts, L
dc.contributor.authorHivert, M-F
dc.contributor.authorNelen, V
dc.contributor.authorPopovic, M
dc.contributor.authorKogevinas, M
dc.contributor.authorNawrot, TS
dc.contributor.authorHerceg, Z
dc.contributor.authorAnnesi-Maesano, I
dc.contributor.authorFallin, MD
dc.contributor.authorYeung, E
dc.contributor.authorBreton, CV
dc.contributor.authorKoletzko, B
dc.contributor.authorHolland, N
dc.contributor.authorWiemels, JL
dc.contributor.authorMelén, E
dc.contributor.authorSharp, GC
dc.contributor.authorSilver, MJ
dc.contributor.authorRezwan, FI
dc.contributor.authorHolloway, JW
dc.date.accessioned2023-10-06T08:21:55Z
dc.date.issued2023-09-11
dc.date.updated2023-10-05T14:49:01Z
dc.description.abstractBACKGROUND: 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.en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council (BBSRC)en_GB
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council (BBSRC)en_GB
dc.description.sponsorshipEuropean Union’s Horizon 2020en_GB
dc.description.sponsorshipEconomic and Social Research Council (ESRC)en_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipEuropean Unionen_GB
dc.description.sponsorshipSwedish foundation for strategic research (SSF)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipEnvironmental Protection Agency (EPA)en_GB
dc.description.sponsorshipNational Cancer Institute Cancer Centeren_GB
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dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipEnvironmental Protection Agency (EPA)en_GB
dc.description.sponsorshipEnvironmental Protection Agency (EPA)en_GB
dc.description.sponsorshipEuropean Unionen_GB
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dc.description.sponsorshipEuropean Union’s Horizon 2020en_GB
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dc.description.sponsorshipGerman Ministry of Education and Researchen_GB
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dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
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dc.description.sponsorshipAutism Speaksen_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipEuropean Unionen_GB
dc.description.sponsorshipEuropean Unionen_GB
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dc.description.sponsorshipEuropean Unionen_GB
dc.description.sponsorshipEuropean Research Council (ERC)en_GB
dc.description.sponsorshipFlemisch Scientific Research Councilen_GB
dc.description.sponsorshipFlemisch Scientific Research Councilen_GB
dc.description.sponsorshipFlemisch Scientific Research Councilen_GB
dc.description.sponsorshipEuropean Unionen_GB
dc.description.sponsorshipFonds de recherche du Québec - Santé (FRQS)en_GB
dc.description.sponsorshipCanadian Institute of Health Research (CIHR)en_GB
dc.description.sponsorshipCanadian Institute of Health Research (CIHR)en_GB
dc.description.sponsorshipNetherlands Organisation for Scientific Research (NWO)en_GB
dc.description.sponsorshipNational Institute of Child and Human Developmenten_GB
dc.description.sponsorshipEuropean Union’s Horizon 2020en_GB
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dc.description.sponsorshipMedical Research Council Integrative Epidemiology Unit (University of Bristol)en_GB
dc.description.sponsorshipNetherlands Heart Foundationen_GB
dc.description.sponsorshipNetherlands Heart Foundationen_GB
dc.description.sponsorshipNetherlands Organisation for Scientific Research (NWO)en_GB
dc.description.sponsorshipEuropean Unionen_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipSpanish Ministry of Scienceen_GB
dc.description.sponsorshipNational Institute for Health and Care Research (NIHR)en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.description.sponsorshipNorwegian Ministry of Health and the Ministry of Education and Researchen_GB
dc.description.sponsorshipNorwegian Ministry of Health and the Ministry of Education and Researchen_GB
dc.description.sponsorshipNorwegian Ministry of Health and the Ministry of Education and Researchen_GB
dc.description.sponsorshipLithuanian Agency for Science Innovation and Technologyen_GB
dc.description.sponsorshipSpanish Ministry of Healthen_GB
dc.description.sponsorshipSpanish Ministry of Healthen_GB
dc.description.sponsorshipSpanish Ministry of Healthen_GB
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dc.description.sponsorshipSpanish Ministry of Healthen_GB
dc.description.sponsorshipInstituto de Salud Carlos IIIen_GB
dc.description.sponsorshipInstituto de Salud Carlos IIIen_GB
dc.description.sponsorshipEuropean Research Council (ERC)en_GB
dc.description.sponsorshipCDMRP/Department of Defenseen_GB
dc.description.sponsorshipNIGMSen_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Asthma Campaign, UKen_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNorwegian Research Councilen_GB
dc.description.sponsorshipNational Institute of Environmental Health Sciencesen_GB
dc.description.sponsorshipResearch Council of Norwayen_GB
dc.description.sponsorshipNational Institute of Environmental Health Sciencesen_GB
dc.description.sponsorshipNational Institute of Environmental Health Sciencesen_GB
dc.description.sponsorshipNational Institute of Diabetes and Digestive and Kidney Diseasesen_GB
dc.description.sponsorshipNational Institute of Environmental Health Sciencesen_GB
dc.description.sponsorshipNational Institute of Environmental Health Sciencesen_GB
dc.description.sponsorshipSwedish Research Councilen_GB
dc.description.sponsorshipSwedish Initiative for research on Microdata in the Social And Medical Sciences (SIMSAM)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipMedical Research Council Integrative Epidemiology Unit (University of Bristol)en_GB
dc.description.sponsorshipMedical Research Council Integrative Epidemiology Unit (University of Bristol)en_GB
dc.description.sponsorshipMedical Research Council Integrative Epidemiology Unit (University of Bristol)en_GB
dc.description.sponsorshipSwedish Heart-Lung Foundationen_GB
dc.description.sponsorshipUniversity of Munichen_GB
dc.description.sponsorshipFoundation for Medical Research (FRM)en_GB
dc.description.sponsorshipNational Agency for Researchen_GB
dc.description.sponsorshipNational Institute for Research in Public Healthen_GB
dc.description.sponsorshipFrench Ministry of Healthen_GB
dc.description.sponsorshipFrench Ministry of Researchen_GB
dc.description.sponsorshipInserm Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programsen_GB
dc.description.sponsorshipParis–Sud Universityen_GB
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dc.description.sponsorshipFrench National Institute for Population Health Surveillanceen_GB
dc.description.sponsorshipFrench National Institute for Health Educationen_GB
dc.description.sponsorshipFrench Agency for Environmental Health Safetyen_GB
dc.description.sponsorshipMutuelle Générale de l’Education Nationaleen_GB
dc.description.sponsorshipFrench National Agency for Food Securityen_GB
dc.description.sponsorshipFrench-speaking association for the study of diabetes and metabolismen_GB
dc.description.sponsorshipItalian National Centre for Disease Prevention and Controlen_GB
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dc.description.sponsorshipGreek Ministry of Healthen_GB
dc.description.sponsorshipFlemish Government (Department of Economy, Science and Innovations, Agency for Care and Health and Department of Environment)en_GB
dc.description.sponsorshipThe Research Foundation-Flandersen_GB
dc.description.sponsorshipFlemish Institute for Technological Researchen_GB
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dc.description.sponsorshipErasmus University Rotterdamen_GB
dc.description.sponsorshipNetherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sporten_GB
dc.description.sponsorshipErasmus MCen_GB
dc.description.sponsorshipDanish National Research Foundationen_GB
dc.description.sponsorshipDanish Regional Committeesen_GB
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dc.description.sponsorshipHelmholtz Center for Environmental Researchen_GB
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dc.format.extent148-
dc.format.mediumElectronic
dc.identifier.citationVol. 15, article 148en_GB
dc.identifier.doihttps://doi.org/10.1186/s13148-023-01542-5
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dc.identifier.urihttp://hdl.handle.net/10871/134180
dc.identifierORCID: 0000-0003-2906-4035 (Sharp, Gemma C)
dc.identifierScopusID: 56898577600 (Sharp, Gemma C)
dc.language.isoenen_GB
dc.publisherBMCen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/37697338en_GB
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.en_GB
dc.subjectBirth seasonen_GB
dc.subjectDNA methylationen_GB
dc.subjectDifferentially methylated regions (DMR)en_GB
dc.subjectLatitudeen_GB
dc.subjectMeta-analysisen_GB
dc.subjectPACEen_GB
dc.titleAnalysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitudeen_GB
dc.typeArticleen_GB
dc.date.available2023-10-06T08:21:55Z
dc.identifier.issn1868-7075
exeter.article-number148
exeter.place-of-publicationGermany
dc.descriptionThis is the final version. Available from BMC via the DOI in this record. en_GB
dc.descriptionIndividual cohort-level data can be obtained from the respective cohort (see Additional file 1: Table S1 and Additional file 2 for cohort details).en_GB
dc.identifier.eissn1868-7083
dc.identifier.journalClinical Epigeneticsen_GB
dc.relation.ispartofClin Epigenetics, 15(1)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2023-07-27
dc.rights.licenseCC BY
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2023-07-27
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2023-10-06T06:49:42Z
refterms.versionFCDVoR
refterms.dateFOA2023-10-06T08:22:45Z
refterms.panelAen_GB
refterms.dateFirstOnline2023-09-11


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© 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.
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