{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:54:21Z","timestamp":1788350061674,"version":"build-2803163510"},"reference-count":38,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"University of Bristol NIHR Biomedical Research Centre","award":["BRC-1215-2001"],"award-info":[{"award-number":["BRC-1215-2001"]}]},{"name":"MRC Integrative Epidemiology Unit","award":["MC_UU_00011\/1"],"award-info":[{"award-number":["MC_UU_00011\/1"]}]},{"name":"CRUK Integrative Cancer Epidemiology Programme","award":["C18281\/A29019"],"award-info":[{"award-number":["C18281\/A29019"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202802\/Z\/16\/Z"],"award-info":[{"award-number":["202802\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Avon Longitudinal Study of Parents and Children","award":["MRC & WT 217065\/Z\/19\/Z"],"award-info":[{"award-number":["MRC & WT 217065\/Z\/19\/Z"]}]},{"name":"the Netherlands Organization for Health Research and Development; ZonMw VIDI","award":["016.136.367"],"award-info":[{"award-number":["016.136.367"]}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR075803"],"award-info":[{"award-number":["R01 AR075803"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The UK Medical Research Council and Wellcome","award":["217065\/Z\/19\/Z"],"award-info":[{"award-number":["217065\/Z\/19\/Z"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:p>\n                    Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the Generation R Study (primary study population, N\n                    <jats:sub>1<\/jats:sub>\n                    \u2009=\u20092,793; mean age of 9.8\u2009y) were correlated with ~30\u2009million genetic variants while adjusting for age, sex, and genomic principal components (proxy for population stratification). Variants associated with DD at genome-wide significant level ( P\u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) mapped to 16q12.2 ( IRX5) (lead variant rs3922616, B\u2009=\u20090.16; P\u2009=\u20092.2\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ). We used Fisher\u2019s combined probability tests weighted by sample size to perform a meta-analysis ( N\u2009=\u200914,805) combining radiographic DD at a mean age of 9.8\u2009y from Generation R with data from a previous GWAS ( N\n                    <jats:sub>2<\/jats:sub>\n                    \u2009=\u200912,012) on number of teeth (NT) in infants used as proxy of DD at a mean age of 9.8\u2009y (including the ALSPAC and NFBC1966). This GWAS meta-analysis revealed 3 novel loci mapping to 7p15.3 ( IGF2BP3: P\u2009=\u20093.2\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ), 14q13.3 ( PAX9: P\u2009=\u20091.9\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ), and 16q12.2 ( IRX5: P\u2009=\u20091.2\u2009\u00d7\u200910\n                    <jats:sup>\u22129<\/jats:sup>\n                    ) and validated 8 previously reported NT loci. A polygenic allele score constructed from these 11 loci was associated with radiographic DD in an independent Generation R set of children ( N\u2009=\u2009703; B\u2009=\u20090.05, P\u2009=\u20090.004). Furthermore, profiling of the identified genes across an atlas of murine and human stem cells observed expression in the cells involved in the formation of bone and\/or dental tissues (&gt;0.3\u2009frequency per kilobase of transcript per million mapped reads), likely reflecting functional specialization. Our findings provide biological insight into the polygenic architecture of the pediatric dental maturation process.\n                  <\/jats:p>","DOI":"10.1177\/00220345221132268","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:54:08Z","timestamp":1669596848000},"page":"349-356","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel Genetic Determinants of Dental Maturation in Children"],"prefix":"10.1177","volume":"102","author":[{"given":"O.","family":"Grgic","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, ErasmusMC, Rotterdam, The Netherlands"},{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9463-3962","authenticated-orcid":false,"given":"V.","family":"Prijatelj","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, ErasmusMC, Rotterdam, The Netherlands"},{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Dudakovic","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3352-3900","authenticated-orcid":false,"given":"S.","family":"Vucic","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, ErasmusMC, Rotterdam, The Netherlands"},{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-067X","authenticated-orcid":false,"given":"B.","family":"Dhamo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, ErasmusMC, Rotterdam, The Netherlands"},{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Trajanoska","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Canada Excellence Research Chair in Genomic Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Monnereau","sequence":"additional","affiliation":[{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4950-1386","authenticated-orcid":false,"given":"M.","family":"Zrimsek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.M.","family":"Gautvik","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Reppe","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7793-7326","authenticated-orcid":false,"given":"S.","family":"Haworth","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"},{"name":"Bristol Dental School, University of Bristol, Bristol, UK"},{"name":"MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.J.","family":"Timpson","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"},{"name":"MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.W.V.","family":"Jaddoe","sequence":"additional","affiliation":[{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.-R.","family":"Jarvelin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Center for Life Course Health Research, University of Oulu, Oulu, Finland"},{"name":"Faculty of Medicine, School of Public Health, Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Evans","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK"},{"name":"Diamantina Institute, The University of Queensland, Brisbane, Australia"},{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.G.","family":"Uitterlinden","sequence":"additional","affiliation":[{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.M.","family":"Ongkosuwito","sequence":"additional","affiliation":[{"name":"Dentistry, Section Orthodontics and Craniofacial Biology, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.J.","family":"van Wijnen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Vermont, Burlington, VT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Medina-Gomez","sequence":"additional","affiliation":[{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Rivadeneira","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, ErasmusMC, Rotterdam, The Netherlands"},{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.B.","family":"Wolvius","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, ErasmusMC, Rotterdam, The Netherlands"},{"name":"The Generation R Study, ErasmusMC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,11,27]]},"reference":[{"key":"bibr1-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2259"},{"key":"bibr2-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.21084"},{"key":"bibr3-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/cjaa056"},{"issue":"2","key":"bibr4-00220345221132268","first-page":"211","volume":"45","author":"Demirjian A","year":"1973","journal-title":"Hum Biol"},{"key":"bibr5-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1177\/00220345800590070301"},{"key":"bibr6-00220345221132268","doi-asserted-by":"publisher","DOI":"10.17305\/bjbms.2018.2841"},{"key":"bibr7-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24852"},{"key":"bibr8-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp497"},{"key":"bibr9-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt231"},{"key":"bibr10-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25020"},{"key":"bibr11-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-017-0342-7"},{"key":"bibr12-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002275"},{"key":"bibr13-00220345221132268","doi-asserted-by":"crossref","first-page":"D514","DOI":"10.1093\/nar\/gki033","volume":"33","author":"Hamosh A","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"bibr14-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1242\/dev.019778"},{"key":"bibr15-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-224"},{"key":"bibr16-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-1486"},{"key":"bibr17-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2012.90"},{"key":"bibr18-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.03.001"},{"key":"bibr19-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1146-8"},{"key":"bibr20-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091807"},{"key":"bibr21-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-015-9998-4"},{"key":"bibr22-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.115076"},{"key":"bibr23-00220345221132268","volume-title":"Ten Cate\u2019s oral histology: development, structure, and function","author":"Nanci A.","year":"2008","edition":"7"},{"key":"bibr24-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2017.10.033"},{"key":"bibr25-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.2.1262"},{"key":"bibr26-00220345221132268","doi-asserted-by":"publisher","DOI":"10.5604\/12321966.1233573"},{"key":"bibr27-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000856"},{"key":"bibr28-00220345221132268","doi-asserted-by":"publisher","DOI":"10.15171\/joddd.2015.0016"},{"key":"bibr29-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"bibr30-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000598"},{"key":"bibr31-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13684"},{"key":"bibr32-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2003.10.031"},{"key":"bibr33-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2018.11.026"},{"key":"bibr34-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2352"},{"key":"bibr35-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"bibr36-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-456"},{"key":"bibr37-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw613"},{"key":"bibr38-00220345221132268","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8876265"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345221132268","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345221132268","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345221132268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:10:09Z","timestamp":1777497009000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345221132268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,27]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1177\/00220345221132268"],"URL":"https:\/\/doi.org\/10.1177\/00220345221132268","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,27]]}}}