A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Shaobo Li; Natalia Spitz; Akram Ghantous; Sarina Abrishamcar; Brigitte Reimann; Irene Marques; Matt J. Silver; Sofía Aguilar-Lacasaña; Negusse Kitaba; Faisal I. Rezwan; Stefan Röder; Lea Sirignano; Johanna Tuhkanen; Giulia Mancano; Gemma C. Sharp; Catherine Metayer; Libby Morimoto; Dan J. Stein; Heather J. Zar; Rossella Alfano; Tim Nawrot; Congrong Wang; Eero Kajantie; Elina Keikkala; Sanna Mustaniemi; Justiina Ronkainen; Sylvain Sebert; Wnurinham Silva; Marja Vääräsmäki; Vincent W.V. Jaddoe; Robin M. Bernstein; Andrew M. Prentice; Marta Cosin-Tomas; Terence Dwyer; Siri Eldevik Håberg; Zdenko Herceg; Maria C. Magnus; Monica Cheng Munthe-Kaas; Christian M. Page; Maja Völker; Maria Gilles; Tabea Send; Stephanie Witt; Lea Zillich; Luigi Gagliardi; Lorenzo Richiardi; Darina Czamara; Katri Räikkönen; Lida Chatzi; Marina Vafeiadi; S. Hasan Arshad; Susan Ewart; Michelle Plusquin; Janine F. Felix; Sophie E. Moore; Martine Vrijheid; John W. Holloway; Wilfried Karmaus; Gunda Herberth; Ana Zenclussen; Fabian Streit; Jari Lahti; Anke Hüls; Thanh T. Hoang; Stephanie J. London; Joseph L. Wiemels

doi:10.1038/s42003-023-05698-x

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Shaobo Li
, Natalia Spitz
, Akram Ghantous
, Sarina Abrishamcar
, Brigitte Reimann
, Irene Marques
, Matt J. Silver
, Sofía Aguilar-Lacasaña
, Negusse Kitaba
, Faisal I. Rezwan
, Stefan Röder
, Lea Sirignano
, Johanna Tuhkanen
, Giulia Mancano
, Gemma C. Sharp
, Catherine Metayer
, Libby Morimoto
, Dan J. Stein
, Heather J. Zar
, Rossella Alfano

Tim Nawrot, Congrong Wang, Eero Kajantie, Elina Keikkala, Sanna Mustaniemi, Justiina Ronkainen, Sylvain Sebert, Wnurinham Silva, Marja Vääräsmäki, Vincent W.V. Jaddoe, Robin M. Bernstein, Andrew M. Prentice, Marta Cosin-Tomas, Terence Dwyer, Siri Eldevik Håberg, Zdenko Herceg, Maria C. Magnus, Monica Cheng Munthe-Kaas, Christian M. Page, Maja Völker, Maria Gilles, Tabea Send, Stephanie Witt, Lea Zillich, Luigi Gagliardi, Lorenzo Richiardi, Darina Czamara, Katri Räikkönen, Lida Chatzi, Marina Vafeiadi, S. Hasan Arshad, Susan Ewart, Michelle Plusquin, Janine F. Felix, Sophie E. Moore, Martine Vrijheid, John W. Holloway, Wilfried Karmaus, Gunda Herberth, Ana Zenclussen, Fabian Streit, Jari Lahti, Anke Hüls, Thanh T. Hoang, Stephanie J. London, Joseph L. Wiemels^*

^*Corresponding author for this work

University of Southern California
International Agency for Research on Cancer
Emory University
Agoralaan
Erasmus University Rotterdam
London School of Hygiene and Tropical Medicine
ISGlobal
Pompeu Fabra University
Centro de Investigación Biomédica en Red
University of Southampton
Aberystwyth University
Helmholtz Centre for Environmental Research
Heidelberg University
University of Helsinki
University of Bristol
University of Exeter
University of California at Berkeley
University of Cape Town
University of Oulu
Norwegian University of Science and Technology
Helsinki University Hospital
National Institute for Health and Welfare
University of Colorado Boulder
University of Oxford
Norwegian Institute of Public Health
University of Oslo
Ospedale Versilia
University of Turin
University of Crete
David Hide Asthma and Allergy Research Centre
Michigan State University
King's College London
University of Memphis
Leipzig University
National Institutes of Health

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

4 Scopus citations

Abstract

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.

Original language	English
Article number	66
Journal	Communications Biology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-05698-x
State	Published - Dec 2024
Externally published	Yes

Funding

Funders	Funder number
National Cancer Institute	R01CA175737
U.S. Environmental Protection Agency	RD83615901, RD83451101
Horizon 2020 Framework Programme	874739
Medical Research Council	MR/T032863/1
National Institute of Environmental Health Sciences	P01ES018172, R01CA185058, R01ES09137

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Li, S., Spitz, N., Ghantous, A., Abrishamcar, S., Reimann, B., Marques, I., Silver, M. J., Aguilar-Lacasaña, S., Kitaba, N., Rezwan, F. I., Röder, S., Sirignano, L., Tuhkanen, J., Mancano, G., Sharp, G. C., Metayer, C., Morimoto, L., Stein, D. J., Zar, H. J., ... Wiemels, J. L. (2024). A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation. Communications Biology, 7(1), Article 66. https://doi.org/10.1038/s42003-023-05698-x

@article{c3cef03e955d452fb909658342adbf2d,

title = "A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation",

abstract = "Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.",

author = "Shaobo Li and Natalia Spitz and Akram Ghantous and Sarina Abrishamcar and Brigitte Reimann and Irene Marques and Silver, \{Matt J.\} and Sof{\'i}a Aguilar-Lacasa{\~n}a and Negusse Kitaba and Rezwan, \{Faisal I.\} and Stefan R{\"o}der and Lea Sirignano and Johanna Tuhkanen and Giulia Mancano and Sharp, \{Gemma C.\} and Catherine Metayer and Libby Morimoto and Stein, \{Dan J.\} and Zar, \{Heather J.\} and Rossella Alfano and Tim Nawrot and Congrong Wang and Eero Kajantie and Elina Keikkala and Sanna Mustaniemi and Justiina Ronkainen and Sylvain Sebert and Wnurinham Silva and Marja V{\"a}{\"a}r{\"a}sm{\"a}ki and Jaddoe, \{Vincent W.V.\} and Bernstein, \{Robin M.\} and Prentice, \{Andrew M.\} and Marta Cosin-Tomas and Terence Dwyer and H{\aa}berg, \{Siri Eldevik\} and Zdenko Herceg and Magnus, \{Maria C.\} and Munthe-Kaas, \{Monica Cheng\} and Page, \{Christian M.\} and Maja V{\"o}lker and Maria Gilles and Tabea Send and Stephanie Witt and Lea Zillich and Luigi Gagliardi and Lorenzo Richiardi and Darina Czamara and Katri R{\"a}ikk{\"o}nen and Lida Chatzi and Marina Vafeiadi and Arshad, \{S. Hasan\} and Susan Ewart and Michelle Plusquin and Felix, \{Janine F.\} and Moore, \{Sophie E.\} and Martine Vrijheid and Holloway, \{John W.\} and Wilfried Karmaus and Gunda Herberth and Ana Zenclussen and Fabian Streit and Jari Lahti and Anke H{\"u}ls and Hoang, \{Thanh T.\} and London, \{Stephanie J.\} and Wiemels, \{Joseph L.\}",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = dec,

doi = "10.1038/s42003-023-05698-x",

language = "אנגלית",

volume = "7",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

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Li, S, Spitz, N, Ghantous, A, Abrishamcar, S, Reimann, B, Marques, I, Silver, MJ, Aguilar-Lacasaña, S, Kitaba, N, Rezwan, FI, Röder, S, Sirignano, L, Tuhkanen, J, Mancano, G, Sharp, GC, Metayer, C, Morimoto, L, Stein, DJ, Zar, HJ, Alfano, R, Nawrot, T, Wang, C, Kajantie, E, Keikkala, E, Mustaniemi, S, Ronkainen, J, Sebert, S, Silva, W, Vääräsmäki, M, Jaddoe, VWV, Bernstein, RM, Prentice, AM, Cosin-Tomas, M, Dwyer, T, Håberg, SE, Herceg, Z, Magnus, MC, Munthe-Kaas, MC, Page, CM, Völker, M, Gilles, M, Send, T, Witt, S, Zillich, L, Gagliardi, L, Richiardi, L, Czamara, D, Räikkönen, K, Chatzi, L, Vafeiadi, M, Arshad, SH, Ewart, S, Plusquin, M, Felix, JF, Moore, SE, Vrijheid, M, Holloway, JW, Karmaus, W, Herberth, G, Zenclussen, A, Streit, F, Lahti, J, Hüls, A, Hoang, TT, London, SJ & Wiemels, JL 2024, 'A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation', Communications Biology, vol. 7, no. 1, 66. https://doi.org/10.1038/s42003-023-05698-x

TY - JOUR

T1 - A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

AU - Li, Shaobo

AU - Spitz, Natalia

AU - Ghantous, Akram

AU - Abrishamcar, Sarina

AU - Reimann, Brigitte

AU - Marques, Irene

AU - Silver, Matt J.

AU - Aguilar-Lacasaña, Sofía

AU - Kitaba, Negusse

AU - Rezwan, Faisal I.

AU - Röder, Stefan

AU - Sirignano, Lea

AU - Tuhkanen, Johanna

AU - Mancano, Giulia

AU - Sharp, Gemma C.

AU - Metayer, Catherine

AU - Morimoto, Libby

AU - Stein, Dan J.

AU - Zar, Heather J.

AU - Alfano, Rossella

AU - Nawrot, Tim

AU - Wang, Congrong

AU - Kajantie, Eero

AU - Keikkala, Elina

AU - Mustaniemi, Sanna

AU - Ronkainen, Justiina

AU - Sebert, Sylvain

AU - Silva, Wnurinham

AU - Vääräsmäki, Marja

AU - Jaddoe, Vincent W.V.

AU - Bernstein, Robin M.

AU - Prentice, Andrew M.

AU - Cosin-Tomas, Marta

AU - Dwyer, Terence

AU - Håberg, Siri Eldevik

AU - Herceg, Zdenko

AU - Magnus, Maria C.

AU - Munthe-Kaas, Monica Cheng

AU - Page, Christian M.

AU - Völker, Maja

AU - Gilles, Maria

AU - Send, Tabea

AU - Witt, Stephanie

AU - Zillich, Lea

AU - Gagliardi, Luigi

AU - Richiardi, Lorenzo

AU - Czamara, Darina

AU - Räikkönen, Katri

AU - Chatzi, Lida

AU - Vafeiadi, Marina

AU - Arshad, S. Hasan

AU - Ewart, Susan

AU - Plusquin, Michelle

AU - Felix, Janine F.

AU - Moore, Sophie E.

AU - Vrijheid, Martine

AU - Holloway, John W.

AU - Karmaus, Wilfried

AU - Herberth, Gunda

AU - Zenclussen, Ana

AU - Streit, Fabian

AU - Lahti, Jari

AU - Hüls, Anke

AU - Hoang, Thanh T.

AU - London, Stephanie J.

AU - Wiemels, Joseph L.

PY - 2024/12

Y1 - 2024/12

N2 - Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.

AB - Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.

UR - https://www.scopus.com/pages/publications/85181721956

U2 - 10.1038/s42003-023-05698-x

DO - 10.1038/s42003-023-05698-x

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C2 - 38195839

AN - SCOPUS:85181721956

SN - 2399-3642

VL - 7

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 66

ER -

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

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