Cord blood epigenome-wide meta-analysis in six European-based child cohorts identifies signatures linked to rapid weight growth
Year: 2023
Type: review
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, Piccolipiù, 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.
Source: BMC Medicine
Authors: Rossella Alfano, Daniela Zugna, Henrique Barros, Mariona Bustamante, Leda Chatzi, Akram Ghantous, Zdenko Herceg, Pekka Keski-Rahkonen, Theo M. de Kok, Tim S Nawrot, Caroline L Relton, Oliver Robinson, Theano Roumeliotaki, Augustin Scalbert, Martine Vrijheid, Paolo Vineis, Lorenzo Richiardi, Michelle Plusquin
Institutions: MRC Centre for Environment and Health, Imperial College London, Hasselt University, Piedmont Reference Center for Epidemiology and Cancer Prevention, University of Turin, Universidade do Porto, Institute of Public Health, University of Porto, Universitat Pompeu Fabra, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, University of Southern California, Centre international de recherche sur le cancer, Maastricht University, University of Bristol, MRC Integrative Epidemiology Unit, University of Crete
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: World Health Organization, Fundació la Marató de TV3, Wellcome Trust, UK Research and Innovation, Centres de Recerca de Catalunya, European Commission, University of Bristol, Generalitat de Catalunya, Fonds Wetenschappelijk Onderzoek, Ministero della Salute, Ministerio de Ciencia e Innovación, Universiteit Hasselt, Directorate for Biological Sciences, HORIZON EUROPE Framework Programme, Medical Research Council, Biotechnology and Biological Sciences Research Council, Instituto de Salud Carlos III, National Institute of Diabetes and Digestive and Kidney Diseases, FP7 Environment
Awards: G1192034430, Enhanced exposure assessment and omic profiling for high priority environmental exposures in Europe, G1402497539, G149876332, G1502031688, Science and Technology in childhood Obesity Policy, G1585958176, G1605161196, G1632783612, G1693598558, G1742557123, G1795554050, G1955001954, G2034942350, G2164340656, G2206155153, G2267092327, G2382355258, G2387096677, G2553663979, G2581098307, G2971175962, G3173997727, G317400622, G3201241063, G3233413551, G3271125737, G3285691745, G3345452146, G3405515844, G3423777635, G3623985979, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3662005835, G3831911591, G3850372127, G4120825843, G4141329914, Accessible resource for integrated epigenomics studies (ARIES), G434337789, Airborne soot particles and neurobiological outcomes: focus on translocation and intermediate mechanisms, G4434902968, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., G452561034, G4578808843, G4749042089, G4909233925, G5000828053, G5001017760, G5107313190, G5159276886, G523383772, G5371351582, G5562631338, G5638830213, Accessible resource for integrated epigenomics studies (ARIES), G5840542394, G586812122, G589846866, G6030688955, G6033091583, G6098864743, G6202791625, G621070573, G6306468304, G6318591655, G6328075693, G6374753769, G6428979846, G6650990183, G6689231961, G6751436026, G702470302, G7078175890, G7095874527, G7250318257, G727641376, Mechanisms of the Development of ALLergy, G738105237, G7552712858, G760317559, G7614373100, G7751898340, G788349370, G801210579, G8303085639, G8782766175, G929055435
OpenAlex ID: W4315487541