ArticleFrontiers in genetics2026
Multivariate GWAS reveals shared genetic basis of common oral diseases.
Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Oral diseases, including dental caries, periodontitis, pulpitis, and temporomandibular disorders (TMD), impose a substantial global burden affecting billions of individuals and costing an estimated USD 390 billion annually. Despite their frequent clinical co-occurrence, the extent to which these conditions share a common genetic basis remains unclear. Methods: We analyzed genome-wide association study (GWAS) summary statistics from up to 500,000 Finnish participants. Genome-wide and regional genetic correlations were quantified using High-Definition Likelihood. Genomic Structural Equation Modelling was applied to identify a latent common oral genetic factor (COF). A multivariate GWAS of the COF was conducted, followed by SuSiE fine-mapping. Integrative gene and pathway analyses were performed using cTWAS and MAGMA, and spatial mapping was conducted using embryonic tooth-germ atlases. Results: We identified extensive shared heritability across all four oral diseases. A latent COF captured the majority of this genetic overlap. Multivariate GWAS of the COF identified 104 genome-wide significant single-nucleotide polymorphisms aggregated into 96 independent loci, which were largely novel compared to single-trait analyses. Fine-mapping refined these to 53 high-confidence causal variants enriched in immune-regulatory and odontogenic pathways. CPSF1 and SLC20A2 emerged as top-ranked genes, with tissue-specific effects mapped to coronary artery and cultured fibroblasts, respectively. Spatial projection localized genetic risk to follicular and mesenchymal compartments, consistent with developmental tissue differentiation patterns. Conclusion: These findings reveal a shared and developmentally rooted genetic architecture underlying common oral diseases. The results highlight convergent molecular mechanisms and provide a foundation for precision-based, integrated prevention strategies that move beyond traditional single-disease frameworks.
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