Abstract
A genome-wide association study of ≈2.5 million markers identified unique biologically informed periodontal complex traits with distinct microbial communities and interleukin-1β (IL-1β) levels. Each trait was associated with different single nucleotide polymorphisms. These variants include genes associated with immune responses, microbial colonization, and the epithelial barrier function. The specific set of variants leads to individual biological paths that converge into an overlapping clinical phenotype of periodontal tissue destruction. This concept suggests that periodontal disease is a group of distinct conditions. We identified polymorphisms in inflammasome genes interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) that were associated with increased severity of periodontal disease. Inflammasomes respond to pathogen or tissue "danger" signals and assemble into multiprotein "machineries" that are essential for the cleavage of proinflammatory mediator IL-1β into an active form. Thus, understanding how variants of IFI16 and AIM2 contribute to periodontal disease pathogenesis may lead to treatment options that address individual biological variations and precision therapies for oral health.