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

Li, SORCID logo; Spitz, NORCID logo; Ghantous, A; Abrishamcar, SORCID logo; Reimann, B; Marques, I; Silver, MJORCID logo; Aguilar-Lacasaña, S; Kitaba, NORCID logo; Rezwan, FIORCID logo; +56 more...Röder, SORCID logo; Sirignano, L; Tuhkanen, J; Mancano, G; Sharp, GC; Metayer, C; Morimoto, LORCID logo; Stein, DJORCID logo; Zar, HJ; Alfano, RORCID logo; Nawrot, T; Wang, C; Kajantie, EORCID logo; Keikkala, E; Mustaniemi, SORCID logo; Ronkainen, JORCID logo; Sebert, SORCID logo; Silva, WORCID logo; Vääräsmäki, M; Jaddoe, VWORCID logo; Bernstein, RM; Prentice, AMORCID logo; Cosin-Tomas, M; Dwyer, TORCID logo; Håberg, SE; Herceg, Z; Magnus, MC; Munthe-Kaas, MC; Page, CM; Völker, M; Gilles, M; Send, T; Witt, SORCID logo; Zillich, LORCID logo; Gagliardi, L; Richiardi, L; Czamara, DORCID logo; Räikkönen, K; Chatzi, L; Vafeiadi, MORCID logo; Arshad, SH; Ewart, S; Plusquin, M; Felix, JFORCID logo; Moore, SE; Vrijheid, MORCID logo; Holloway, JWORCID logo; Karmaus, WORCID logo; Herberth, GORCID logo; Zenclussen, AORCID logo; Streit, FORCID logo; Lahti, JORCID logo; Hüls, A; Hoang, TTORCID logo; London, SJORCID logo; Wiemels, JLORCID logo and (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). 66-. ISSN 2399-3642 DOI: 10.1038/s42003-023-05698-x
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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.


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