@article{ef136c09da9c4b8f9bb81bc6207f2630,
title = "Cord blood epigenome-wide meta-analysis in six European-based child cohorts identifies signatures linked to rapid weight growth",
abstract = "Background Rapid postnatal growth may result from exposure in utero or early life to adverse conditions and has been associated with diseases later in life and, in particular, with childhood obesity. DNA methylation, interfacing early-life exposures and subsequent diseases, is a possible mechanism underlying early-life programming.Methods Here, a meta-analysis of Illumina HumanMethylation 450K/EPIC-array associations of cord blood DNA methylation at single CpG sites and CpG genomic regions with rapid weight growth at 1 year of age (defined with reference to WHO growth charts) was conducted in six European-based child cohorts (ALSPAC, ENVIRONAGE, Generation XXI, INMA, Piccolipiu, and RHEA, N = 2003). The association of gestational age acceleration (calculated using the Bohlin epigenetic clock) with rapid weight growth was also explored via meta-analysis. Follow-up analyses of identified DNA methylation signals included prediction of rapid weight growth, mediation of the effect of conventional risk factors on rapid weight growth, integration with transcriptomics and metabolomics, association with overweight in childhood (between 4 and 8 years), and comparison with previous findings.Results Forty-seven CpGs were associated with rapid weight growth at suggestive p-value < 1e-05 and, among them, three CpGs (cg14459032, cg25953130 annotated to ARID5B, and cg00049440 annotated to KLF9) passed the genome-wide significance level (p-value < 1.25e-07). Sixteen differentially methylated regions (DMRs) were identified as associated with rapid weight growth at false discovery rate (FDR)-adjusted/Siddak p-values < 0.01. Gestational age acceleration was associated with decreasing risk of rapid weight growth (p-value = 9.75e-04). Identified DNA methylation signals slightly increased the prediction of rapid weight growth in addition to conventional risk factors. Among the identified signals, three CpGs partially mediated the effect of gestational age on rapid weight growth. Both CpGs (N=3) and DMRs (N=3) were associated with differential expression of transcripts (N=10 and 7, respectively), including long non-coding RNAs. An AURKC DMR was associated with childhood overweight. We observed enrichment of CpGs previously reported associated with birthweight.Conclusions Our findings provide evidence of the association between cord blood DNA methylation and rapid weight growth and suggest links with prenatal exposures and association with childhood obesity providing opportunities for early prevention.",
keywords = "Rapid weight growth, Weight gain, DNA methylation, Gestational age acceleration, Childhood overweight, AURKC, Gene expression, DNA METHYLATION, BIRTH-WEIGHT, MATERNAL SMOKING, OBESITY, ASSOCIATION, PREGNANCY, PROFILE, MOTHER, EXPRESSION, VARIANTS",
author = "R. Alfano and D. Zugna and H. Barros and M. Bustamante and L. Chatzi and A. Ghantous and Z. Herceg and P. Keski-Rahkonen and {de Kok}, T.M. and T.S. Nawrot and C.L. Relton and O. Robinson and T. Roumeliotaki and A. Scalbert and M. Vrijheid and P. Vineis and L. Richiardi and M. Plusquin",
note = "Funding Information: ALSPAC was provided core support by the United Kingdom Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol. The Accessible Resource for Integrated Epigenomics Studies (ARIES) which generated large-scale methylation data was funded by the United Kingdom Biotechnology and Biological Sciences Research Council (BB/I025751/1 and BB/I025263/1). Additional epigenetic profiling on the ALSPAC cohort was supported by the United Kingdom Medical Research Council Integrative Epidemiology Unit and the University of Bristol (MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, and MC_UU_12013_8), the Wellcome Trust (WT088806), and the United States National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK10324). Funding Information: The GXXI cohort is funded by Programa Operacional de Sa{\'u}de – Sa{\'u}de XXI, Quadro Comunit{\'a}rio de Apoio III and Administra{\c c}{\~a}o Regional de Sa{\'u}de Norte (Regional Department of Ministry of Health). Funding Information: The Piccolipi{\`u} cohort was initially supported by the Italian National Center for Disease Prevention and Control (CCM grants years 2010 and 2014) and by the Italian Ministry of Health (art 12 and 12 bis D.lgs 502/92). Funding Information: This INMA study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundaci{\'o} La marat{\'o} de TV3 (090430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. Funding Information: Cohort-specific acknowledgments can be found in Additional file 1 : Supplementary Methods [27 –38]. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. Funding Information: This work is supported by the Bijzonder Onderzoeksfonds Hasselt University through a PhD fellowship [to RA], by the UKRI Future Leaders Fellowship [MR/S03532X/1, to OR], by the European FP7 Grant to “EXPOsOMICS” project [Grant ref 308610], and by the European Commission Horizon 2020 Grant to the “STOP Project” [Grant ref 774548]. Funding Information: The ENVIRONAGE birth cohort is supported by the European Research Council [ERC-2012-StG.310898] and by funds of the Flemish Scientific Research council [FWO, G.073315N, G059219N]. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = jan,
day = "11",
doi = "10.1186/s12916-022-02685-7",
language = "English",
volume = "21",
journal = "BMC Medicine",
issn = "1741-7015",
publisher = "BioMed Central Ltd",
number = "1",
}