Genome-wide association study of periodontitis severity and progression.

BACKGROUND: To add to the knowledge base of periodontal genomics, we carried out a genome-wide association study (GWAS) of periodontitis severity and progression among 416 mixed-ethnicity adult participants of a periodontitis clinical study.

METHODS: Participants were 168 adults (mean age = 50 years, 46% males) with severe periodontitis and 248 adults (mean age = 48 years, 40% males) without severe periodontitis, including 147 with mild periodontitis and 101 periodontally healthy. Disease progression information over a 12-month period was available for 368 of these participants. Single marker discovery analysis relied on logistic regression models adjusted for age, sex, and genetically determined ancestry using a conventional p < 5x10-8 genome-wide statistical significance criterion. Genome-wide significant loci were annotated and examined for associations with periodontal disease traits in external cohorts of 10,019 Hispanic/Latinos, 4,554 European Americans, and 973 African Americans.

RESULTS: All GWAS single nucleotide polymorphisms (SNPs) explained 34% of phenotypic variance between periodontitis cases and controls and 57% of the variance in disease progression in this study. We identified 2 genome-wide significant loci associated with disease progression (SUMO2P2, small ubiquitin-like modifier 2, rs72691774, p = 1.9x10-8] and CUBN (cubilin, rs565051161, p = 3.9x10-8). CUBN was strongly associated with periodontal disease in the independent samples of African Americans (rs7082270, p = 3.1x10-7) and Hispanic/Latinos (rs1276710, p = 1.5x10-5), albeit the lead SNPs were rare and differed in each population. Meanwhile, ZBTB16 (zinc finger and BTB domain-containing 16) showed the strongest evidence of association with severe periodontitis (rs454802, p = 2.2x10-7).

CONCLUSIONS: This study's results emanate from a well-characterized cohort of periodontitis severity and progression and add to the knowledge base of periodontal genomics and the underlying individual disease susceptibility.

PLAIN LANGUAGE SUMMARY: This study assessed the association of gene variants in association with gum disease severity and progression in 416 participants of a clinical study. Participants were 168 adults (mean age = 50 years, 46% males) with severe disease and 248 adults (mean age = 48 years, 40% males) without severe disease, including 147 with mild disease and 101 without disease. Disease progression information over a 12-month period was available for 368 of these participants. Single marker discovery analysis relied on logistic regression models adjusted for age, sex, and genetically determined ancestry. Genome-wide significant loci were annotated and examined for associations with periodontal disease traits in external cohorts of 10,019 Hispanic/Latinos, 4,554 European Americans, and 973 African Americans. All gene variants explained 34% of the variance between cases and controls and 57% of the variance in disease progression in this study. We identified 2 genome-wide significant loci associated with disease progression (SUMO2P2 and CUBN). CUBN was strongly associated with periodontal disease in the independent samples of African Americans and Hispanic/Latinos. ZBTB16 showed the strongest evidence of association with severe periodontitis. This study's results emanate from a well-characterized cohort of periodontitis severity and progression, suggest that about one-third of variance in disease severity and over half of variance in disease progression are attributable to individual susceptibility, and add to the knowledge base of periodontal genomics.