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Cord blood epigenome-wide meta-analysis in six European-based child cohorts identifies signatures linked to rapid weight growth.
Alfano, Rossella; Zugna, Daniela; Barros, Henrique; Bustamante, Mariona; Chatzi, Leda; Ghantous, Akram; Herceg, Zdenko; Keski-Rahkonen, Pekka; de Kok, Theo M; Nawrot, Tim S; Relton, Caroline L; Robinson, Oliver; Roumeliotaki, Theano; Scalbert, Augustin; Vrijheid, Martine; Vineis, Paolo; Richiardi, Lorenzo; Plusquin, Michelle.
Afiliação
  • Alfano R; Medical Research Council Centre for Environment and Health, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.
  • Zugna D; Centre for Environmental Sciences, Hasselt University, Agoralaan Building D, 3590, Diepenbeek, Belgium.
  • Barros H; Department of Medical Sciences, University of Turin and CPO-Piemonte, Turin, Italy.
  • Bustamante M; Institute of Public Health, University of Porto, Porto, Portugal.
  • Chatzi L; ISGlobal, Institute of Global Health, Barcelona, Spain.
  • Ghantous A; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Herceg Z; CIBER Epidemiología y Salud Pública, Madrid, Spain.
  • Keski-Rahkonen P; Department of Preventive Medicine, University of Southern California, Los Angeles, USA.
  • de Kok TM; International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
  • Nawrot TS; International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
  • Relton CL; International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
  • Robinson O; Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
  • Roumeliotaki T; Centre for Environmental Sciences, Hasselt University, Agoralaan Building D, 3590, Diepenbeek, Belgium.
  • Scalbert A; Μedical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Vrijheid M; Medical Research Council Centre for Environment and Health, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.
  • Vineis P; Mohn Centre for Children's Health and Well-being, The School of Public Health, Imperial College London, London, UK.
  • Richiardi L; Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.
  • Plusquin M; International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
BMC Med ; 21(1): 17, 2023 01 11.
Article em En | MEDLINE | ID: mdl-36627699
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Obesidade Infantil / Epigenoma Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Child / Female / Humans / Pregnancy Idioma: En Revista: BMC Med Assunto da revista: MEDICINA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Obesidade Infantil / Epigenoma Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Child / Female / Humans / Pregnancy Idioma: En Revista: BMC Med Assunto da revista: MEDICINA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Reino Unido