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

Abstract

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 105 genome-wide significant loci, including 47 previously unreported associations. 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. HLA analyses implicated DQA1 and DQB1 alleles in lichen planus and other mucosal disorders. We observed 378 statistically significant genetic correlations among oral traits, such as tooth loss and chronic apical periodontitis (rg = 0.91, 95% CI [0.76 - 1.05], P = 1.73 x 10-34), and 419 significant correlations between oral and systemic diseases, including periodontal diseases with chronic laryngitis (rg = 0.97, CI [0.58 - 1.36], P = 1.23 x 10-6) and bruxism with gastro-oesophageal reflux (rg = 0.51, CI [0.38 - 0.65], P = 1.10 x 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.