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Previous genetic studies were limited by small sample sizes and low genomic coverage. To address these limitations, we conducted a genome-wide association study (GWAS) using array-based genotype data in 5 large, multiancestral cohorts. The study included 3,405 participants from the United States and its territories, the Philippines, Colombia, and Nigeria. Class II malocclusion was defined as an Angle\u2019s class II molar relationship with an overjet &gt;3.5 mm, class III malocclusion as an Angle\u2019s class III molar relationship with a negative overjet, and class I malocclusion (controls) as an Angle\u2019s class I molar relationship with an overjet of 0 to 3.5 mm. In the vertical plane, an anterior open bite of any magnitude was classified as \u201copen bite,\u201d while an overbite &gt;3.5 mm was classified as \u201cdeep bite,\u201d with controls having an overbite of 0 to 3.5 mm. Multiplanar malocclusion included cases with both sagittal and vertical discrepancies, with controls having an Angle\u2019s class I molar relationship, an overjet of 0 to 3.5 mm, and an overbite of 0 to 3.5 mm. GWAS for each phenotype was conducted within individual cohorts before meta-analysis. We identified genome-wide significant associations (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2264 5E-08) at 11q22.3 (rs372564249, odds ratio [OR] = 3.12) and 3p24.3 (rs13060317, OR = 2.4) for class II and multiplanar malocclusion, respectively. Additionally, we observed a near-significant signal at 12q15 (rs1261646, OR = 1.9,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 6.2 \u00d7 10\n                    <jats:sup>-8<\/jats:sup>\n                    ) for class II malocclusion and a suggestive association at 1p21.3 (rs7541224, OR = 2.0,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 1.7 \u00d7 10\n                    <jats:sup>-7<\/jats:sup>\n                    ) for class III malocclusion. The 11q22.3 and 3p24.3 loci were QTLs for the\n                    <jats:italic toggle=\"yes\">PDGFD<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">SGO1-AS1<\/jats:italic>\n                    genes, and transcriptomic data showed consistent expression of these genes during facial development. These findings provide valuable insights into malocclusion etiology and lay the groundwork for genetic risk score development.\n                  <\/jats:p>","DOI":"10.1177\/00220345261442129","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:37:02Z","timestamp":1781591822000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiancestral GWAS of Dental Malocclusion Identifies Multiple Risk Loci"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-0221","authenticated-orcid":false,"given":"A.","family":"Alade","sequence":"first","affiliation":[{"name":"Craniofacial Anomalies and Regeneration Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.M.","family":"Maurer","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Anderton","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.-K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Almpani","sequence":"additional","affiliation":[{"name":"Craniofacial Anomalies and Regeneration Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Goovaerts","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, KU Leuven, Leuven, Belgium"},{"name":"Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Claes","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, KU Leuven, Leuven, Belgium"},{"name":"Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium"},{"name":"Department of Electrical Engineering, ESAT\/PSI, KU Leuven, Leuven, Belgium"},{"name":"Murdoch Children\u2019s Research Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-5964","authenticated-orcid":false,"given":"A.","family":"Butali","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA, USA"},{"name":"The Iowa Institute for Oral Health Research, College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Adeyemo","sequence":"additional","affiliation":[{"name":"Centre for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA, USA"},{"name":"The Iowa Institute for Oral Health Research, College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"J.K.","family":"Hartsfield","sequence":"additional","affiliation":[{"name":"Center of Oral Health Research and Department of Oral Health Science, Division of Orthodontics, College of Dentistry, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0439-3000","authenticated-orcid":false,"given":"L.A.","family":"Morford","sequence":"additional","affiliation":[{"name":"Center of Oral Health Research and Department of Oral Health Science, Division of Orthodontics, College of Dentistry, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Peter","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0766-8455","authenticated-orcid":false,"given":"D.W.","family":"McNeil","sequence":"additional","affiliation":[{"name":"Department of Community Dentistry and Behavioral Science, University of Florida College of Dentistry, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1897-1131","authenticated-orcid":false,"given":"J.R.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6682-238X","authenticated-orcid":false,"given":"B.","family":"Foxman","sequence":"additional","affiliation":[{"name":"Center for Molecular and Clinical Epidemiology of Infectious Diseases &amp; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.M.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.M.","family":"Moreno Uribe","sequence":"additional","affiliation":[{"name":"Department of 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