A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.
Shaobo LiNatália SpitzAkram GhantousSarina AbrishamcarBrigitte ReimannIrene MarquesPrachand IssarapuSofía Aguilar-LacasañaNegusse Tadesse KitabaFaisal I RezwanStefan RöderLea SirignanoJohanna TuhkanenGiulia MancanoGemma C SharpCatherine MetayerLibby M MorimotoDan J SteinHeather J ZarRossella AlfanoTim NawrotCongrong WangKajantie EeroElina KeikkalaSanna MustaniemiJustiina RonkainenSylvain SebertWnurinham SilvaMarja VääräsmäkiVincent W V JaddoeRobin M BernsteinAndrew M PrenticeMarta Cosin-TomasTerence DwyerSiri Eldevik HåbergZdenko HercegMaria C MagnusMonica Cheng Munthe-KaasChristian M PageMaja VölkerMaria GillesTabea SendStephanie-H WittLea ZillichLuigi GagliardiLorenzo RichiardiDarina CzamaraKatri RäikkönenLida ChatziMarina VafeiadiS Hasan ArshadSusan EwartMichelle PlusquinJanine F FelixSophie E MooreMartine VrijheidJohn W HollowayWilfried J J KarmausGunda HerberthAna Claudia ZenclussenFabian StreitJari M T LahtiAnke HülsThanh T HoangStephanie J LondonJoseph L WiemelsPublished in: Communications biology (2024)
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.
Keyphrases
- dna methylation
- gestational age
- genome wide
- gene expression
- preterm birth
- pregnancy outcomes
- blood pressure
- systematic review
- low birth weight
- copy number
- electronic health record
- young adults
- childhood cancer
- type diabetes
- big data
- risk factors
- transcription factor
- machine learning
- air pollution
- metabolic syndrome
- human health
- preterm infants
- randomized controlled trial
- risk assessment
- atomic force microscopy
- deep learning