{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:20:45Z","timestamp":1790554845645,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":2490,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007\u20102013"],"award-info":[{"award-number":["FP7\/2007\u20102013"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/P028179\/1"],"award-info":[{"award-number":["BB\/P028179\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["201268\/Z\/16\/Z"],"award-info":[{"award-number":["201268\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Poor intrauterine and childhood growth has been linked with the risk of osteoporosis in later life, a relationship that may in part be mediated through altered epigenetic regulation of genes. We previously identified a region within the promoter of the long non-coding RNA ANRIL encoded by the CDKN2A locus, at which differential DNA methylation at birth showed correlations with offspring adiposity. Given the common lineage of adipocytes and osteoblasts, we investigated the relationship between perinatal CDKN2A methylation and bone mass at ages 4 and 6 years. Using sodium bisulfite pyrosequencing, we measured the methylation status of the 9 CpGs within this region in umbilical cord samples from discovery (n\u2009=\u2009332) and replication (n\u2009=\u2009337) cohorts of children from the Southampton Women's Survey, whose bone mass was assessed by dual-energy X-ray absorptiomietry (DXA; Hologic Discovery). Inverse associations were found between perinatal CDKN2A methylation and whole-body minus head bone area (BA), bone mineral content (BMC), and areal bone mineral density (BMD). This was confirmed in replication and combined data sets (all p\u2009&amp;lt;\u20090.01), with each 10% increase in methylation being associated with a decrease in BMC of 4 to 9\u2009g at age 4 years (p\u2009\u2264\u20090.001). Relationships were similar with 6-year bone mass. Functional investigation of the differentially methylated region in the SaOS-2 osteosarcoma cell line showed that transcription factors bound to the identified CpGs in a methylation-specific manner and that CpG mutagenesis modulated ANRIL expression. In conclusion, perinatal methylation at CDKN2A is associated with childhood bone development and has significance for cell function. \u00a9 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3153","type":"journal-article","created":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T14:02:53Z","timestamp":1492437773000},"page":"2030-2040","source":"Crossref","is-referenced-by-count":40,"title":["Perinatal DNA Methylation at <i>CDKN2A<\/i> Is Associated With Offspring Bone Mass: Findings From the Southampton Women's Survey"],"prefix":"10.1093","volume":"32","author":[{"given":"Elizabeth M","family":"Curtis","sequence":"first","affiliation":[{"name":"MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Murray","sequence":"additional","affiliation":[{"name":"Institute of Developmental SciencesUniversity of 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SouthamptonSouthamptonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel","family":"Inskip","sequence":"additional","affiliation":[{"name":"NIHR Southampton Biomedical Research CentreUniversity of Southampton and University Hospital Southampton NHS Foundation TrustSouthamptonUK"},{"name":"MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith M","family":"Godfrey","sequence":"additional","affiliation":[{"name":"NIHR Southampton Biomedical Research CentreUniversity of Southampton and University Hospital Southampton NHS Foundation TrustSouthamptonUK"},{"name":"Institute of Developmental SciencesUniversity of SouthamptonSouthamptonUK"},{"name":"MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G","family":"Bell","sequence":"additional","affiliation":[{"name":"Centre for Biological SciencesUniversity of SouthamptonSouthamptonUK"},{"name":"Institute of Developmental SciencesUniversity of SouthamptonSouthamptonUK"},{"name":"MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Cooper","sequence":"additional","affiliation":[{"name":"NIHR Oxford Musculoskeletal Biomedical Research UnitUniversity of OxfordOxfordUK"},{"name":"NIHR Southampton Biomedical Research CentreUniversity of Southampton and University Hospital Southampton NHS Foundation TrustSouthamptonUK"},{"name":"MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A","family":"Lillycrop","sequence":"additional","affiliation":[{"name":"Centre for Biological SciencesUniversity of SouthamptonSouthamptonUK"},{"name":"NIHR Southampton Biomedical Research CentreUniversity of Southampton and University Hospital Southampton NHS 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