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

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Kadalayil, Latha

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Alam, Md Zahangir

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White, Cory Haley

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Ghantous, Akram

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Walton, Esther

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Gruzieva, Olena

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Merid, Simon Kebede

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Kumar, Ashish

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Roy, Ritu P

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Solomon, Olivia

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Huen, Karen

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Eskenazi, Brenda

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Rzehak, Peter

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Grote, Veit

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Langhendries, Jean-Paul

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Verduci, Elvira

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Ferre, Natalia

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Gruszfeld, Darek

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Gao, Lu

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Guan, Weihua

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Zeng, Xuehuo

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Schisterman, Enrique F

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Dou, John F

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Bakulski, Kelly M

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Feinberg, Jason I

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Soomro, Munawar Hussain

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Pesce, Giancarlo

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Baiz, Nour

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Isaevska, Elena

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Plusquin, Michelle

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Vafeiadi, Marina

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Roumeliotaki, Theano

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Langie, Sabine AS

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Standaert, Arnout

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Allard, Catherine

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Perron, Patrice

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Bouchard, Luigi

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van Meel, Evelien R

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Felix, Janine F

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Jaddoe, Vincent WV

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Yousefi, Paul D

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Ramlau-Hansen, Cecilia H

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Relton, Caroline L

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Tobi, Elmar W

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Starling, Anne P

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Yang, Ivana V

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Llambrich, Maria

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Santorelli, Gillian

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Lepeule, Johanna

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Salas, Lucas A

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Bustamante, Mariona

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Ewart, Susan L

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Zhang, Hongmei

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Karmaus, Wilfried

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Röder, Stefan

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Zenclussen, Ana Claudia

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Jin, Jianping

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Nystad, Wenche

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Page, Christian M

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Magnus, Maria

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Jima, Dereje D

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Hoyo, Cathrine

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Maguire, Rachel L

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Kvist, Tuomas

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Czamara, Darina

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Räikkönen, Katri

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Gong, Tong

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Ullemar, Vilhelmina

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Rifas-Shiman, Sheryl L

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Oken, Emily

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Almqvist, Catarina

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Karlsson, Robert

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Lahti, Jari

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Murphy, Susan K

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Håberg, Siri E

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London, Stephanie

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Herberth, Gunda

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Arshad, Hasan

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Sunyer, Jordi

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Grazuleviciene, Regina

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Dabelea, Dana

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Steegers-Theunissen, Régine PM

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Nohr, Ellen A

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Sørensen, Thorkild IA

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Duijts, Liesbeth

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Hivert, Marie-France

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Nelen, Vera

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Popovic, Maja

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Kogevinas, Manolis

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Nawrot, Tim S

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Herceg, Zdenko

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Annesi-Maesano, Isabella

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Fallin, M Daniele

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Yeung, Edwina

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Breton, Carrie V

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Koletzko, Berthold

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Holland, Nina

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Wiemels, Joseph L

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Melén, Erik

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Sharp, Gemma C

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Silver, Matt J

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Rezwan, Faisal I

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Holloway, John W

dc.date.accessioned

2024-03-27T16:33:06Z

dc.date.available

2024-03-27T16:33:06Z

dc.date.issued

2023-09

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.identifier

10.1186/s13148-023-01542-5

dc.identifier.issn

1868-7075

dc.identifier.issn

1868-7083

dc.identifier.uri

https://hdl.handle.net/10161/30400

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Clinical epigenetics

dc.relation.isversionof

10.1186/s13148-023-01542-5

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.subject

Humans

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Asthma

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Inflammation

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Seasons

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DNA Methylation

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Child

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Child, Preschool

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Infant

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Infant, Newborn

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Carcinogenesis

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Murphy, Susan K|0000-0001-8298-7272

pubs.begin-page

148

pubs.issue

1

pubs.organisational-group

Duke

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Nicholas School of the Environment

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School of Medicine

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Clinical Science Departments

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Institutes and Centers

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Obstetrics and Gynecology

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Pathology

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Duke Cancer Institute

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Environmental Sciences and Policy

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Obstetrics and Gynecology, Reproductive Sciences

pubs.publication-status

Published

pubs.volume

15

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