Exploring the genetic basis of chronic periodontitis: a genome-wide approach Public Deposited

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  • March 20, 2019
Creator
  • Divaris, Kimon
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Chronic periodontitis (CP) is a common-complex oral disease that affects the majority of the adult population and is a major cause of tooth loss. The disease is characterized by an oral biofilm pathological shift that contributes to cascade of events leading to periodontal destruction. Factors modulating the establishment of a dysbiotic oral microbiome or affecting the host immunity and inflammatory response are promising preventive and therapeutic targets. Although a substantial genetic component of CP is theorized and numerous candidate-gene studies have been completed, to-date no wholegenome association (GWA) studies have been performed. We performed a GWA analysis of CP in well-defined cohort of 4500 white subjects who were participants of the Atherosclerosis Risk In Communities study. Traits of interest were the three-level disease CDC/AAP classification (healthy/mild, moderate, severe CP) and a continuous extent of disease [proportion of sites exhibiting ≥3 mm attachment loss (EAL)] measure. Additionally, we examined three traits of high bacterial colonization defined as the highest quintile of the distribution of “red” and “orange” complex bacteria, and Aggregatibacter actinomycetemcomitans that were quantified using DNA-DNA checkerboard hybridization in a subset of 1020 white study subjects. Genotyping was performed using the Affymetrix 6.0 platform. Imputation to 2.5million markers was based on HapMap II-CEU and a multiple-test corrected significance threshold was applied (P<5x10-8). We detected no genome-wide significant signals. However, we found suggestive evidence of association (P<5x10-6) for CP with ten loci including NPY, NIN, WNT5A for severe, NCR2, EMR1 for moderate CP, and TBX18, ETS1, DYNC2H1, TTC26 and ZC3HAV1 for EAL. Additionally, thirteen loci including KCNK1, FBXO38, IL33, RUNX2, CAMTA1 and VAMP3 provided suggestive signals of association (P<5x10-6) with the examined “high” bacterial colonization traits. The NPY (7p15) locus was replicated in an independent cohort of whites of European descent. These genome-wide scan results from a large well-defined cohort provide information on multiple candidate regions for interrogation in genetic studies of CP. Future investigations providing further replication of these findings may lead to an improved understanding of the complex nature of host-biofilm and -bacteria interactions that characterizes states of health and disease.
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  • "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department Epidemiology of the Gillings School of Global Public Health."
Advisor
  • Olshan, Andrew
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  • Chapel Hill, NC
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  • Open access
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