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DNA methylation, interfacing early-life exposures and subsequent diseases, is a possible mechanism underlying early-life programming.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>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, ENVIR<jats:italic>ON<\/jats:italic>AGE, Generation XXI, INMA, Piccolipi\u00f9, and RHEA, <jats:italic>N<\/jats:italic> = 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Forty-seven CpGs were associated with rapid weight growth at suggestive <jats:italic>p<\/jats:italic>-value &lt;1e\u221205 and, among them, three CpGs (cg14459032, cg25953130 annotated to <jats:italic>ARID5B<\/jats:italic>, and cg00049440 annotated to <jats:italic>KLF9<\/jats:italic>) passed the genome-wide significance level (<jats:italic>p<\/jats:italic>-value &lt;1.25e\u221207). Sixteen differentially methylated regions (DMRs) were identified as associated with rapid weight growth at false discovery rate (FDR)-adjusted\/Siddak <jats:italic>p<\/jats:italic>-values &lt; 0.01. Gestational age acceleration was associated with decreasing risk of rapid weight growth (<jats:italic>p<\/jats:italic>-value = 9.75e\u221204). 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 (<jats:italic>N<\/jats:italic>=3) and DMRs (<jats:italic>N<\/jats:italic>=3) were associated with differential expression of transcripts (<jats:italic>N<\/jats:italic>=10 and 7, respectively), including long non-coding RNAs. An <jats:italic>AURKC<\/jats:italic> DMR was associated with childhood overweight. We observed enrichment of CpGs previously reported associated with birthweight.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12916-022-02685-7","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T02:02:31Z","timestamp":1673402551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cord blood epigenome-wide meta-analysis in six European-based child cohorts identifies signatures linked to rapid weight growth"],"prefix":"10.1186","volume":"21","author":[{"given":"Rossella","family":"Alfano","sequence":"first","affiliation":[]},{"given":"Daniela","family":"Zugna","sequence":"additional","affiliation":[]},{"given":"Henrique","family":"Barros","sequence":"additional","affiliation":[]},{"given":"Mariona","family":"Bustamante","sequence":"additional","affiliation":[]},{"given":"Leda","family":"Chatzi","sequence":"additional","affiliation":[]},{"given":"Akram","family":"Ghantous","sequence":"additional","affiliation":[]},{"given":"Zdenko","family":"Herceg","sequence":"additional","affiliation":[]},{"given":"Pekka","family":"Keski-Rahkonen","sequence":"additional","affiliation":[]},{"given":"Theo M.","family":"de Kok","sequence":"additional","affiliation":[]},{"given":"Tim S","family":"Nawrot","sequence":"additional","affiliation":[]},{"given":"Caroline L","family":"Relton","sequence":"additional","affiliation":[]},{"given":"Oliver","family":"Robinson","sequence":"additional","affiliation":[]},{"given":"Theano","family":"Roumeliotaki","sequence":"additional","affiliation":[]},{"given":"Augustin","family":"Scalbert","sequence":"additional","affiliation":[]},{"given":"Martine","family":"Vrijheid","sequence":"additional","affiliation":[]},{"given":"Paolo","family":"Vineis","sequence":"additional","affiliation":[]},{"given":"Lorenzo","family":"Richiardi","sequence":"additional","affiliation":[]},{"given":"Michelle","family":"Plusquin","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"2685_CR1","volume-title":"Obesity: preventing and managing the global epidemic: report of a WHO consultation","author":"WHO Consultation on Obesity (1999: Geneva, Switzerland) & World Health Organization","year":"2000","unstructured":"WHO Consultation on Obesity (1999: Geneva, Switzerland) & World Health Organization. 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Ethical approval for the studies was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees for ALSPAC study with initial approval given by the Bristol and Weston Health Authority: E1808 Children of the Nineties: ALSPAC (28\/11\/1989), the Southmead Health Authority: 49\/89 Children of the Nineties -\u201cALSPAC\u201d (5\/04\/1990) and the Frenchay Health Authority: 90\/8 Children of the Nineties (28\/06\/1990) (full details are available on the study website ); the Ethical Committee of Hasselt University and the East-Limburg Hospital for ENVIR<i>ON<\/i>AGE study (B371201216090); the ethics committee of the Hospital del Mar Medical Research Institute for INMA (2005\/2106\/I); for Piccolipi\u00f9 study, the Ethics Committees of the Local Health Unit Roma E (management center, protocol 11\/11 approved on 24\/05\/2011) and the local Ethics Committee of each center, including the Turin center that contribute to this study (Ethical Committee of the University Hospital \u201cCitt\u00e0 della Salute e della Scienza di Torino\u201d and the Hospital \u201cOrdine Mauriziano di Torino,\u201d protocol 383 approved on 24\/10\/2011); the Ethics Committee of the University Hospital at Heraklion for Rhea study; and the Ethical Committee of S\u00e3o Jo\u00e3o Hospital\/University of Porto Medical School for the GXXI study (authorization n. 5833\/2011).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}