Genomic Landscape of Apical Periodontitis

We undertook the first genome-wide association (GWAS) study of apical periodontitis, enrolling 932 patients with deep carious lesions at UTHealth School of Dentistry and the University of Pittsburgh School of Dental Medicine. We used a case-control design to compare those with apical periodontitis to those without. Genotype data was generated for all participants and imputed using the TOPMed reference panel. We performed a single-variant association testing, a subphenotype analysis, and a genetically regulated expression association analysis, and generated a polygenic risk score and performed phenome-wide association analysis. We identified eight near-genome-wide significant loci for our primary outcome, eight genes where genetically regulated expression was associated with apical periodontitis status, and 33 phecodes that were associated with the generated polygenic risk score. We also replicated three loci previously reported in the literature. Genotype, phenotype, and results from the primary association analysis will be available via dbGaP.]]>
Inclusion Criteria:Age >= 18 yearsUndergoing treatment at UTHealth School of Dentistry or the University of Pittsburgh School of Dental MedicineHaving deep carious lesion(s) (involving >= 2/3 of dentin depth)Exclusion Criteria: Previous endodontic treatment of the tooth of interestHaving any medical condition that requires the use of systemic modifiers of bone metabolism, systemic antibiotics, anti-inflammatory medications, or hormone therapy during six months leading up to study entrySmokingPreexisting periodontal disease]]>