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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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s42003-023-05698-x
Publication website:
https://pure.eur.nl/ws/files/126115179/s42003-023-05698-x.pdf

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Author
ORCID:
0000-0002-0544-5338
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Role:
Author
ORCID:
0000-0003-4776-1758
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ORCID:
0000-0002-2582-6402
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ORCID:
0000-0001-9478-7374
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Author
ORCID:
0000-0003-3634-4633


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Funder identifier:
10.13039/100000139
Grant:
RD83451101
RD83615901


Publisher:
Nature Research
Journal:
Communications Biology More from this journal
Volume:
7
Issue:
1
Pages:
66-66
Article number:
66
Publication date:
2024-01-09
DOI:
EISSN:
2399-3642
ISSN:
2399-3642


Language:
English
Keywords:
Pubs id:
1602694
Local pid:
pubs:1602694
Source identifiers:
W4390764867
Deposit date:
2026-06-05
ARK identifier:
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