A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.
A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.
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DOI：
10.1038/s42003-023-05698-x
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发表时间：
2024-01-09
影响因子：
5.9
通讯作者：
Wiemels, Joseph L.
中科院分区：
文献类型：
--
作者：
Li, Shaobo;Spitz, Natalia;Ghantous, Akram;Abrishamcar, Sarina;Reimann, Brigitte;Marques, Irene;Silver, Matt J.;Aguilar-Lacasana, Sofia;Kitaba, Negusse;Rezwan, Faisal I.;Roeder, Stefan;Sirignano, Lea;Tuhkanen, Johanna;Mancano, Giulia;Sharp, Gemma C.;Metayer, Catherine;Morimoto, Libby;Stein, Dan J.;Zar, Heather J.;Alfano, Rossella;Nawrot, Tim;Wang, Congrong;Kajantie, Eero;Keikkala, Elina;Mustaniemi, Sanna;Ronkainen, Justiina;Sebert, Sylvain;Silva, Wnurinham;Vaarasmaki, Marja;Jaddoe, Vincent W. V.;Bernstein, Robin M.;Prentice, Andrew M.;Cosin-Tomas, Marta;Dwyer, Terence;Haberg, Siri Eldevik;Herceg, Zdenko;Magnus, Maria C.;Munthe-Kaas, Monica Cheng;Page, Christian M.;Voelker, Maja;Gilles, Maria;Send, Tabea;Witt, Stephanie;Zillich, Lea;Gagliardi, Luigi;Richiardi, Lorenzo;Czamara, Darina;Raikkonen, Katri;Chatzi, Lida;Vafeiadi, Marina;Arshad, S. Hasan;Ewart, Susan;Plusquin, Michelle;Felix, Janine F.;Moore, Sophie E.;Vrijheid, Martine;Holloway, John W.;Karmaus, Wilfried;Herberth, Gunda;Zenclussen, Ana;Streit, Fabian;Lahti, Jari;Huls, Anke;Hoang, Thanh T.;London, Stephanie J.;Wiemels, Joseph L.
较高的出生顺序与许多疾病状态的风险改变有关。连续妊娠时胎盘位置的改变和对宫内生长因子的暴露可能通过持续的DNA甲基化改变影响以后的疾病风险。我们用Illumina DNA甲基化阵列数据研究了16个出生队列(8164名新生儿)中每个人的出生顺序，这些人的祖先来自妊娠和儿童表观遗传学联合会的欧洲人、非洲人和拉丁裔。Meta分析数据显示，341个CpG(FDR调整后的P <； )和1107个区域存在系统性甲基化变异。40个CpG位于血液中基因表达性状的已知数量性状基因座内，性状丰富分析表明与免疫相关、转录调控和血压调节表型有很强的相关性。世界范围内生育率的下降，以及伴随而来的第一个孩子比例的增加，突显了与出生顺序相关的表观基因组状态对疾病发病率趋势变化的潜在反映。一项大规模的多队列关联研究揭示了出生顺序对基因组周围DNA甲基化事件的强烈和一致的影响，这可能是由于第一次和第二次怀孕之间胎盘、营养和生长因素的变化。
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. A large-scale multi-cohort association study reveals strong and consistent impacts of birth order on DNA methylation events around the genome, potentially due to changes in placentation, nutrition, and growth factors between first and subsequent pregnancies.
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