{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:39:30Z","timestamp":1792521570905,"version":"4.5.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["U01DE025046"],"award-info":[{"award-number":["U01DE025046"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["X01HG010871"],"award-info":[{"award-number":["X01HG010871"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:p>\n                    Early childhood caries (ECC) is the most common noncommunicable childhood disease\u2014an important health problem with known environmental and social\/behavioral influences lacking consensus genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multiancestry population of U.S. preschool-age children ( N\u2009=\u20096,103) ages 3 to 5 y participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used International Caries Detection and Assessment System criteria to measure ECC; the primary trait was the number of primary tooth surfaces with caries experience (i.e., dmfs index). We estimated heritability and concordance rates and conducted genome-wide association analyses to estimate overall genetic effects as well as stratified by sex, household water fluoride, and dietary sugar and leveraged combined gene\/gene-environment effects using 2-degree-of-freedom joint tests. Common genetic variants explained 24% of ECC phenotypic variance among unrelated individuals, while concordance rates were 0.64 (95% confidence interval [CI]\u2009=\u20090.42\u20130.79) among monozygotic twins and 0.44 (95% CI\u2009=\u20090.34\u20130.53) among first-degree relatives. Across all analyses, we identified 21 novel nonoverlapping genome-wide significant loci ( P\u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) and 1 genome-wide significant gene ( TAAR6) associated with ECC. The taste receptor activity gene set, with known roles in chemosensing, bacterial recognition, and innate immunity in the oral cavity, was strongly associated with ECC. While no locus remained significant after studywise multiple-testing correction, 3 loci were nominally significant ( P\u2009&lt;\u20090.05) and directionally consistent in external cohorts of 285,248 adults (rs1442369, DLGAP1 and rs74606067, RP11-856F16.2) and 18,994 children (rs71327750, SLC41A3). Meanwhile, the strongest marker known to be associated with adult caries (rs1122171, tagging the long noncoding RNA PITX1-AS1) was nominally significant ( P\u2009=\u20090.01) and directionally consistent with ECC in our study. Taken together, the results of this study add to the genomics knowledge base for early childhood caries, offer several plausible candidates for future mechanistic studies, and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations.\n                  <\/jats:p>","DOI":"10.1177\/00220345241291528","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T05:49:03Z","timestamp":1734587343000},"page":"280-289","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Multiancestry Genome-Wide Association Study of Early Childhood Caries"],"prefix":"10.1177","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-082X","authenticated-orcid":false,"given":"P.","family":"Shrestha","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, NC, USA"},{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Graff","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"},{"name":"Department of Statistics and Actuarial Science, School of Computing and Data Science, The University of Hong Kong, Pokfulam Road, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.L.","family":"Avery","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ginnis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.A.","family":"Simancas-Pallares","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.G.","family":"Ferreira Zandon\u00e1","sequence":"additional","affiliation":[{"name":"Department of Comprehensive Care, School of Dental Medicine, Tufts University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.N.","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Orlova","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine; Department of Human Genetics, School of Public Health; University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.S.","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.N.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, NC, USA"},{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.M.","family":"Highland","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.S.","family":"Preisser","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.D.","family":"Slade","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry and Dental Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.L.","family":"Marazita","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine; 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