Multiancestral GWAS of Dental Malocclusion Identifies Multiple Risk Loci

A Alade; J M Maurer; J Anderton; M-K Lee; K Almpani; S Goovaerts; P Claes; A Butali; A Adeyemo; S Levy; J K Hartsfield Jr; L A Morford; T Peter; S Miller; D W McNeil; J R Shaffer; B Foxman; S M Weinberg; L M Moreno Uribe; M L Marazita; J S Lee

doi:10.1177/00220345261442129

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Multiancestral GWAS of Dental Malocclusion Identifies Multiple Risk Loci

Journal article

Peer reviewed

Multiancestral GWAS of Dental Malocclusion Identifies Multiple Risk Loci

A Alade, J M Maurer, J Anderton, M-K Lee, K Almpani, S Goovaerts, P Claes, A Butali, A Adeyemo, S Levy, …

Journal of dental research

06/15/2026

DOI: 10.1177/00220345261442129

PMID: 42298958

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Abstract

Malocclusion is a common oral health problem with a strong hereditary component. 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’s class II molar relationship with an overjet >3.5 mm, class III malocclusion as an Angle’s class III molar relationship with a negative overjet, and class I malocclusion (controls) as an Angle’s 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 “open bite,” while an overbite >3.5 mm was classified as “deep bite,” 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’s 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 (P ≤ 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, P = 6.2 × 10-8) for class II malocclusion and a suggestive association at 1p21.3 (rs7541224, OR = 2.0, P = 1.7 × 10-7) for class III malocclusion. The 11q22.3 and 3p24.3 loci were QTLs for the PDGFD and SGO1-AS1 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.

SNPs

transcriptomics

Face

Overbite/Openbite

Angle Class II

Angle Class III

Details

Title: Subtitle: Multiancestral GWAS of Dental Malocclusion Identifies Multiple Risk Loci
Creators: A Alade - National Institute of Dental and Craniofacial Research
J M Maurer - University of Pittsburgh
J Anderton - University of Pittsburgh
M-K Lee - University of Pittsburgh
K Almpani - National Institute of Dental and Craniofacial Research
S Goovaerts - KU Leuven
P Claes - Murdoch Children's Research Institute
A Butali - University of Iowa
A Adeyemo - National Institutes of Health
S Levy - University of Iowa, Preventive and Community Dentistry
J K Hartsfield Jr - University of Kentucky
L A Morford - University of Kentucky
T Peter - University of Iowa
S Miller - University of Illinois Chicago
D W McNeil - University of Florida
J R Shaffer - University of Pittsburgh
B Foxman - University of Michigan
S M Weinberg - University of North Carolina at Chapel Hill
L M Moreno Uribe - University of Iowa
M L Marazita - University of Pittsburgh
J S Lee - National Institute of Dental and Craniofacial Research
Resource Type: Journal article
Publication Details: Journal of dental research
DOI: 10.1177/00220345261442129
PMID: 42298958
NLM abbreviation: J Dent Res
ISSN: 1544-0591
eISSN: 1544-0591
Publisher: Sage
Grant note: NIH/NIDCR national institutes of health: R01-DE014899
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by research grants from the National Institutes of Health: R01-DE016148 (M.L.M., S.W.M.), R01-DE032122 (J.R.S., M.L.M., S.W.M.), and X01-HG011437 (J.R.S., M.L.M.), which funded the POFC2 study; R01-DE014899 (M.L.M., D.W.M., B.F., J.R.S.) and U01-DE018903 (M.L.M.) for COHRA1/DentalSCORE; R01-DE014899 (M.L.M., D.W.M., B.F., J.R.S.) and X01-HG009878 (J.R.S.) for COHRA2; and U01-DE018903 (M.L.M.), U01-DE028522 (S.L.), and R01-DE09551 (S.L.) for IFS.
Language: English
Electronic publication date: 06/15/2026
Academic Unit: Preventive and Community Dentistry; Orthodontics; Oral Pathology, Radiology and Medicine; Stead Family Department of Pediatrics; Epidemiology; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9985175478702771

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