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Multiancestral GWAS of Dental Malocclusion Identifies Multiple Risk Loci
A Alade1, J M Maurer2, J Anderton2
1Craniofacial Anomalies and Regeneration Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, Bethesda, MD, USA.
Journal of Dental Research
|June 16, 2026
Summary
This study identified novel genetic loci for malocclusion, including class II and multiplanar types, using a large genome-wide association study (GWAS). Findings highlight specific genes involved in facial development, paving the way for genetic risk scores in oral health.
Area of Science:
- Genetics and Genomics
- Oral and Maxillofacial Surgery
- Orthodontics
Background:
- Malocclusion, a prevalent oral health condition, has a significant hereditary basis.
- Previous genetic investigations were constrained by limited sample sizes and genomic coverage.
- Addressing these limitations is crucial for understanding malocclusion's genetic architecture.
Purpose of the Study:
- To conduct a comprehensive genome-wide association study (GWAS) to identify genetic variants associated with malocclusion.
- To investigate genetic factors contributing to different malocclusion phenotypes, including Class II, Class III, open bite, deep bite, and multiplanar malocclusion.
- To explore the role of identified genetic loci in facial development.
Main Methods:
- A genome-wide association study (GWAS) was performed using array-based genotype data from 3,405 participants across five large, multiancestral cohorts.
- Phenotypic definitions included specific criteria for Angle's classification, overjet, and overbite to categorize malocclusion types.
- Meta-analysis of GWAS results from individual cohorts was conducted to identify genome-wide significant associations (P ≤ 5E-08).
Main Results:
- Genome-wide significant associations were identified at 11q22.3 (rs372564249, OR=3.12) for Class II malocclusion and 3p24.3 (rs13060317, OR=2.4) for multiplanar malocclusion.
- A near-significant association was observed at 12q15 (rs1261646, OR=1.9) for Class II malocclusion, and a suggestive association at 1p21.3 (rs7541224, OR=2.0) for Class III malocclusion.
- The identified loci at 11q22.3 and 3p24.3 are quantitative trait loci (QTLs) for PDGFD and SGO1-AS1 genes, respectively, with consistent expression during facial development.
Conclusions:
- This large-scale GWAS provides novel insights into the genetic underpinnings of malocclusion.
- The identified genetic loci and associated genes (PDGFD, SGO1-AS1) offer potential targets for understanding malocclusion etiology.
- These findings lay the foundation for developing genetic risk scores to aid in the prediction and management of malocclusion.
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