TY - JOUR
T1 - Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude
AU - Kadalayil, Latha
AU - Alam, Md Zahangir
AU - White, Cory Haley
AU - Ghantous, Akram
AU - Walton, Esther
AU - Gruzieva, Olena
AU - Merid, Simon Kebede
AU - Kumar, Ashish
AU - Roy, Ritu P.
AU - Solomon, Olivia
AU - Huen, Karen
AU - Eskenazi, Brenda
AU - Rzehak, Peter
AU - Grote, Veit
AU - Langhendries, Jean Paul
AU - Verduci, Elvira
AU - Ferre, Natalia
AU - Gruszfeld, Darek
AU - Gao, Lu
AU - Guan, Weihua
AU - Zeng, Xuehuo
AU - Schisterman, Enrique F.
AU - Dou, John F.
AU - Bakulski, Kelly M.
AU - Feinberg, Jason I.
AU - Soomro, Munawar Hussain
AU - Pesce, Giancarlo
AU - Baiz, Nour
AU - Isaevska, Elena
AU - Plusquin, Michelle
AU - Vafeiadi, Marina
AU - Roumeliotaki, Theano
AU - Langie, Sabine A.S.
AU - Standaert, Arnout
AU - Allard, Catherine
AU - Perron, Patrice
AU - Bouchard, Luigi
AU - van Meel, Evelien R.
AU - Felix, Janine F.
AU - Jaddoe, Vincent W.V.
AU - Yousefi, Paul D.
AU - Ramlau-Hansen, Cecilia H.
AU - Relton, Caroline L.
AU - Tobi, Elmar W.
AU - Starling, Anne P.
AU - Yang, Ivana V.
AU - Llambrich, Maria
AU - Santorelli, Gillian
AU - Lepeule, Johanna
AU - Salas, Lucas A.
AU - Holloway, J. W.
AU - Et al.
N1 - Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.
PY - 2023/9/11
Y1 - 2023/9/11
N2 - 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.
AB - 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.
KW - Birth season
KW - Differentially methylated regions (DMR)
KW - DNA methylation
KW - Latitude
KW - Meta-analysis
KW - PACE
U2 - 10.1186/s13148-023-01542-5
DO - 10.1186/s13148-023-01542-5
M3 - Article
SN - 1868-7083
VL - 15
JO - Clinical epigenetics
JF - Clinical epigenetics
IS - 1
M1 - 148
ER -