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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.

SUBMITTER: Li S

PROVIDER: S-EPMC10776586 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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

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

Communications biology 20240109 1

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 syste ...[more]

PMID: 38195839

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Project description:BackgroundLateral ventricular volume (LVV) enlargement has been repeatedly linked to schizophrenia; yet, what biological factors shape LVV during early development remain unclear. DNA methylation (DNAm), an essential process for neurodevelopment that is altered in schizophrenia, is a key molecular system of interest.MethodsIn this study, we conducted the first epigenome-wide association study of neonatal DNAm in cord blood with LVV in childhood (measured using T1-weighted brain scans at 10 years), based on data from a large population-based birth cohort, the Generation R Study (N = 840). Employing both probe-level and methylation profile score (MPS) approaches, we further examined whether epigenetic modifications identified at birth in cord blood are: (a) also observed cross-sectionally in childhood using peripheral blood DNAm at age of 10 years (Generation R, N = 370) and (b) prospectively associated with LVV measured in young adulthood in an all-male sample from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 114).ResultsAt birth, DNAm levels at four CpGs (annotated to potassium channel tetramerization domain containing 3, KCTD3; SHH signaling and ciliogenesis regulator, SDCCAG8; glutaredoxin, GLRX) prospectively associated with childhood LVV after genome-wide correction; these genes have been implicated in brain development and psychiatric traits including schizophrenia. An MPS capturing a broader epigenetic profile of LVV - but not individual top hits - showed significant cross-sectional associations with LVV in childhood in Generation R and prospectively associated with LVV in early adulthood within ALSPAC.ConclusionsThis study finds suggestive evidence that DNAm at birth prospectively associates with LVV at different life stages, albeit with small effect sizes. The prediction of MPS on LVV in a childhood sample and an independent male adult sample further underscores the stability and reproducibility of DNAm as a potential marker for LVV. Future studies with larger samples and comparable time points across development are needed to further elucidate how DNAm associates with this clinically relevant brain structure and risk for neuropsychiatric disorders, and what factors explain the identified DNAm profile of LVV at birth.

Project description:Psychosocial stress during pregnancy has been associated with adverse pregnancy outcomes including preterm birth (PTB). This has not been studied in Puerto Rico, an area with high PTB rates. Our objective was to develop a conceptual model describing the interrelationships between measures of psychosocial stress and depression, a result of stress, among pregnant women in Puerto Rico and to examine their associations with PTB. We used data from the Puerto Rico Testsite for Exploring Contamination Threats pregnancy cohort (PROTECT, N = 1,047) to examine associations among depression and different continuous measures of psychosocial stress using path analysis. Psychosocial stress during pregnancy was assessed using validated measures of perceived stress, negative life experiences, neighborhood perceptions and social support. Logistic regression was used to examine associations between psychosocial stress measures in tertiles and PTB. Perceived stress, negative life experiences, and neighborhood perceptions influenced depression through multiple pathways. Our model indicated that perceived stress had the strongest direct effect on depression, where one standard deviation (SD) increase in perceived stress was associated with a 57% SD increase in depression. Negative life experiences were directly but also indirectly, through perceived stress, associated with depression. Finally, neighborhood perceptions directly influenced negative life experiences and perceived stress and consequently had an indirect effect on depression. Psychosocial stress was not associated with PTB across any of the measures examined. Our study examined interrelationships between multiple measures of psychosocial stress and depression among a pregnant Puerto Rican population and identified negative neighborhood perceptions as important upstream factors leading to depression. Our findings highlight the complex relationship between psychosocial stress measures and indicate that psychosocial stress and depression, assessed using 5 different scales, were not associated with PTB. Future research should investigate other environmental and behavioral risk factors contributing to higher rates of PTB in this population.

Dataset Information

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

Publications

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

Similar Datasets

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