Genetic architecture of 67 oral diseases and their links to systemic diseases.

Oral and craniofacial diseases are common, yet their genetic basis and links to systemic health are incompletely understood. We performed genome-wide association analyses of 67 oral phenotypes in 500,348 FinnGen participants, identifying 102 genome-wide significant loci, including 45 previously unreported associations. 48 loci remained significant after category-level Bonferroni correction. Fine-mapping revealed 14 coding variants, such as a missense variant in USP31 for caries and in MANBA for oral leukoplakia, and a stop-gained variant in GPNMB for temporomandibular disorders. Human leukocyte antigen (HLA) analyses implicated DQA1 and DQB1 alleles in lichen planus and other mucosal disorders. We observed 378 statistically significant genetic correlations (rg) among oral traits, such as tooth loss and chronic apical periodontitis (rg = 0.91, 95% confidence interval [CI]: [0.76, 1.05], p = 1.7 × 10-34), and 419 significant correlations between oral and systemic diseases, including periodontal diseases with chronic laryngitis (rg = 0.97, 95% CI: [0.58, 1.36], p = 1.2 × 10-6) and bruxism with gastroesophageal reflux (rg = 0.51, 95% CI: [0.38, 0.65], p = 1.1 × 10-13). These results expand the catalog of oral disease loci, uncover Finnish-enriched risk alleles, and highlight shared inflammatory, immune, and structural pathways connecting oral and systemic health.