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

PACE consortium

doi:10.1186/s13148-023-01542-5

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

PACE consortium

Research output: Contribution to journal › Article › peer-review

2 Citations (SciVal)

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.

Original language	English
Article number	148
Journal	CLINICAL EPIGENETICS
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s13148-023-01542-5
Publication status	Published - 11 Sept 2023

Bibliographical note

The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors LK will serve as guarantor for the contents of this paper.
A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by BBI025751/1 and BB/I025263/1, MC_UU_12013/1 & MC_UU_12013/2 & MC_UU_12013/8. EW is funded by the European Union’s Horizon 2020 research and innovation programme (EarlyCause, grant nº 848158) and by CLOSER (grant reference: ES/K000357/1). GCS is financially supported by the Medical Research Council [New Investigator Research Grant, MR/S009310/1] and the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1].

Keywords

Birth season
DNA methylation
Differentially methylated regions (DMR)
Latitude
Meta-analysis
PACE

ASJC Scopus subject areas

Genetics(clinical)
Genetics
Molecular Biology
Developmental Biology

Access to Document

10.1186/s13148-023-01542-5Licence: CC BY

Cite this

@article{542f2eb3004b4bf9b6e0b4c9954db5d0,

title = "Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude",

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.",

keywords = "Birth season, DNA methylation, Differentially methylated regions (DMR), Latitude, Meta-analysis, PACE",

author = "{PACE consortium} and Latha Kadalayil and Alam, {Md Zahangir} and White, {Cory Haley} and Akram Ghantous and Esther Walton and Olena Gruzieva and Merid, {Simon Kebede} and Ashish Kumar and Roy, {Ritu P} and Olivia Solomon and Karen Huen and Brenda Eskenazi and Peter Rzehak and Veit Grote and Jean-Paul Langhendries and Elvira Verduci and Natalia Ferre and Darek Gruszfeld and Lu Gao and Weihua Guan and Xuehuo Zeng and Schisterman, {Enrique F} and Dou, {John F} and Bakulski, {Kelly M} and Feinberg, {Jason I} and Soomro, {Munawar Hussain} and Giancarlo Pesce and Nour Baiz and Elena Isaevska and Michelle Plusquin and Marina Vafeiadi and Theano Roumeliotaki and Langie, {Sabine A S} and Arnout Standaert and Catherine Allard and Patrice Perron and Luigi Bouchard and {van Meel}, {Evelien R} and Felix, {Janine F} and Jaddoe, {Vincent W V} and Yousefi, {Paul D} and Ramlau-Hansen, {Cecilia H} and Relton, {Caroline L} and Tobi, {Elmar W} and Starling, {Anne P} and Yang, {Ivana V} and Maria Llambrich and Gillian Santorelli and Johanna Lepeule and Salas, {Lucas A}",

note = "The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors LK will serve as guarantor for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by BBI025751/1 and BB/I025263/1, MC_UU_12013/1 & MC_UU_12013/2 & MC_UU_12013/8. EW is funded by the European Union{\textquoteright}s Horizon 2020 research and innovation programme (EarlyCause, grant nº 848158) and by CLOSER (grant reference: ES/K000357/1). GCS is financially supported by the Medical Research Council [New Investigator Research Grant, MR/S009310/1] and the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1]. ",

year = "2023",

month = sep,

day = "11",

doi = "10.1186/s13148-023-01542-5",

language = "English",

volume = "15",

journal = "CLINICAL EPIGENETICS",

issn = "1868-7075",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude

AU - PACE consortium

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

N1 - The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors LK will serve as guarantor for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by BBI025751/1 and BB/I025263/1, MC_UU_12013/1 & MC_UU_12013/2 & MC_UU_12013/8. EW is funded by the European Union’s Horizon 2020 research and innovation programme (EarlyCause, grant nº 848158) and by CLOSER (grant reference: ES/K000357/1). GCS is financially supported by the Medical Research Council [New Investigator Research Grant, MR/S009310/1] and the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1].

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 - DNA methylation

KW - Differentially methylated regions (DMR)

KW - Latitude

KW - Meta-analysis

KW - PACE

UR - http://www.scopus.com/inward/record.url?scp=85170627066&partnerID=8YFLogxK

U2 - 10.1186/s13148-023-01542-5

DO - 10.1186/s13148-023-01542-5

M3 - Article

C2 - 37697338

SN - 1868-7075

VL - 15

JO - CLINICAL EPIGENETICS

JF - CLINICAL EPIGENETICS

IS - 1

M1 - 148

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

EarlyCause

Cite this