Genome-wide association study of periodontitis severity and progression

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.

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.

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).

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.

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.