{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T17:03:42Z","timestamp":1794243822029,"version":"4.9.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000317","name":"Action Medical Research","doi-asserted-by":"publisher","award":["GN2880"],"award-info":[{"award-number":["GN2880"]}],"id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biomedical Research Centre, Oxford"},{"DOI":"10.13039\/100007028","name":"The Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council"},{"name":"National Health Service"},{"name":"National Institute for Health\u00a0and Care\u00a0Research"},{"name":"CCUK"},{"DOI":"10.13039\/100018353","name":"ECCO","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"EC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The genetic contribution to inflammatory bowel disease (IBD), encompassing both Crohn\u2019s disease (CD) and ulcerative colitis (UC), accounts for around 20% of disease variance, highlighting the need to characterize environmental and epigenetic influences. Recently, considerable progress has been made in characterizing the adult methylome in epigenome-wide association studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD and UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We derived and validated a 4-probe methylation biomarker (RPS6KA2, VMP1, CFI, and ARHGEF3), with specificity and high diagnostic accuracy for pediatric IBD in UK and North American cohorts (area under the curve: 0.90-0.94). Significant epigenetic age acceleration is present at diagnosis, with the greatest observed in CD patients. Cis-methylation quantitative trait loci (meQTL) analysis identifies genetic determinants underlying epigenetic alterations notably within the HLA 6p22.1-p21.33 region. Passive smoking exposure is associated with the development of UC rather than CD, contrary to previous findings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data provide new insights into epigenetic alterations in IBD and illustrate the reproducibility and translational potential of epigenome-wide association studies in complex diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjae157","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T12:41:37Z","timestamp":1728045697000},"source":"Crossref","is-referenced-by-count":3,"title":["The Circulating Methylome in Childhood-Onset Inflammatory Bowel Disease"],"prefix":"10.1093","author":[{"given":"Alexandra","family":"Noble","sequence":"first","affiliation":[{"name":"Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford , 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,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal","family":"Nayak","sequence":"additional","affiliation":[{"name":"Addenbrooke\u2019s Hospital Department of Paediatrics, University of Cambridge, , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling","family":"Quinn","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Kristiansen","sequence":"additional","affiliation":[{"name":"UCL Genomics, Great Ormond Street Institute of Child Health, University College London , London 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Nutrition, Cambridge University Hospitals (CUH), Addenbrooke\u2019s Hospital Department of Paediatric Gastroenterology, , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamara","family":"Jayamanne","sequence":"additional","affiliation":[{"name":"John Radcliffe Hospital, Oxford University Hospital NHS Trust Department of Paediatrics, , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3944-6646","authenticated-orcid":false,"given":"Richard","family":"Hansen","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee Department of Child Health, , Dundee ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7573-3397","authenticated-orcid":false,"given":"Georgina L","family":"Hold","sequence":"additional","affiliation":[{"name":"Microbiome 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