{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:29:53Z","timestamp":1773930593681,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n To add to the knowledge base of periodontal genomics, we carried out a genome\u2010wide association study (GWAS) of periodontitis severity and progression among 416 mixed\u2010ethnicity adult participants of a periodontitis clinical study.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Participants were 168 adults (mean age\u00a0=\u00a050 years, 46% males) with severe periodontitis and 248 adults (mean age\u00a0=\u00a048 years, 40% males) without severe periodontitis, including 147 with mild periodontitis and 101 periodontally healthy. Disease progression information over a 12\u2010month period was available for 368 of these participants. Single marker discovery analysis relied on logistic regression models adjusted for age, sex, and genetically determined ancestry using a conventional\n p\u00a0<\/jats:italic>\n <\u00a05x10\n \u22128<\/jats:sup>\n genome\u2010wide statistical significance criterion. Genome\u2010wide significant loci were annotated and examined for associations with periodontal disease traits in external cohorts of 10,019 Hispanic\/Latinos, 4,554 European Americans, and 973 African Americans.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n All GWAS single nucleotide polymorphisms (SNPs) explained 34% of phenotypic variance between periodontitis cases and controls and 57% of the variance in disease progression in this study. We identified 2 genome\u2010wide significant loci associated with disease progression (\n SUMO2P2<\/jats:italic>\n , small ubiquitin\u2010like modifier 2, rs72691774,\n p<\/jats:italic>\n \u00a0=\u00a01.9x10\n \u22128<\/jats:sup>\n ] and\n CUBN<\/jats:italic>\n (cubilin, rs565051161,\n p<\/jats:italic>\n \u00a0=\u00a03.9x10\n \u22128<\/jats:sup>\n ).\n CUBN<\/jats:italic>\n was strongly associated with periodontal disease in the independent samples of African Americans (rs7082270,\n p\u00a0<\/jats:italic>\n =\u00a03.1x10\n \u22127<\/jats:sup>\n ) and Hispanic\/Latinos (rs1276710,\n p<\/jats:italic>\n \u00a0=\u00a01.5x10\n \u22125<\/jats:sup>\n ), albeit the lead SNPs were rare and differed in each population. Meanwhile,\n ZBTB16<\/jats:italic>\n (zinc finger and BTB domain\u2010containing 16) showed the strongest evidence of association with severe periodontitis (rs454802,\n p\u00a0<\/jats:italic>\n =\u00a02.2x10\n \u22127<\/jats:sup>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study's results emanate from a well\u2010characterized cohort of periodontitis severity and progression and add to the knowledge base of periodontal genomics and the underlying individual disease susceptibility.<\/jats:p>\n <\/jats:sec>\n \n Plain language summary<\/jats:title>\n \n This study assessed the association of gene variants in association with gum disease severity and progression in 416 participants of a clinical study. Participants were 168 adults (mean age\u00a0=\u00a050 years, 46% males) with severe disease and 248 adults (mean age\u00a0=\u00a048 years, 40% males) without severe disease, including 147 with mild disease and 101 without disease. Disease progression information over a 12\u2010month period was available for 368 of these participants. Single marker discovery analysis relied on logistic regression models adjusted for age, sex, and genetically determined ancestry. Genome\u2010wide significant loci were annotated and examined for associations with periodontal disease traits in external cohorts of 10,019 Hispanic\/Latinos, 4,554 European Americans, and 973 African Americans. All gene variants explained 34% of the variance between cases and controls and 57% of the variance in disease progression in this study. We identified 2 genome\u2010wide significant loci associated with disease progression (\n SUMO2P2<\/jats:italic>\n and\n CUBN<\/jats:italic>\n ).\n CUBN<\/jats:italic>\n was strongly associated with periodontal disease in the independent samples of African Americans and Hispanic\/Latinos.\n ZBTB16<\/jats:italic>\n showed the strongest evidence of association with severe periodontitis. This study's results emanate from a well\u2010characterized cohort of periodontitis severity and progression, suggest that about one\u2010third of variance in disease severity and over half of variance in disease progression are attributable to individual susceptibility,\u00a0and add to the knowledge base of periodontal genomics.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jper.70017","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T09:06:39Z","timestamp":1765962399000},"page":"247-258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome\u2010wide association study of periodontitis severity and progression"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6945-9811","authenticated-orcid":false,"given":"Flavia","family":"Teles","sequence":"first","affiliation":[{"name":"Department of Basic & Translational Sciences School of Dental Medicine University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Center for Innovation and Precision Dentistry University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6161-6921","authenticated-orcid":false,"given":"Ganesh","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Basic & Translational Sciences School of Dental Medicine University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-082X","authenticated-orcid":false,"given":"Poojan","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry and Dental Public Health Adams School of Dentistry University of North Carolina\u2010Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2332-1774","authenticated-orcid":false,"given":"Kevin","family":"Moss","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Sciences School of Medicine Indiana University Indianapolis Indiana USA"},{"name":"Department of Biomedical Sciences Adams School of Dentistry University of North Carolina\u2010Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Patel","sequence":"additional","affiliation":[{"name":"The Forsyth Institute Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Kallan","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-3156","authenticated-orcid":false,"given":"Camila","family":"Furquim","sequence":"additional","affiliation":[{"name":"Department of Basic & Translational Sciences School of Dental Medicine University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Periodontology and Oral Implantology Dental Research Division University of Guarulhos Guarulhos S\u00e3o Paulo 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