Biologically Defined or Biologically Informed Traits Are More Heritable Than Clinically Defined Ones: The Case of Oral and Dental Phenotypes

  • Cary S. Agler
  • Kevin Moss
  • Kamaira H. Philips
  • Julie T. Marchesan
  • Miguel Simancas-Pallares
  • James D. Beck
  • Kimon DivarisEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1197)


The genetic basis of oral health has long been theorized, but little information exists on the heritable variance in common oral and dental disease traits explained by the human genome. We sought to add to the evidence base of heritability of oral and dental traits using high-density genotype data in a well-characterized community-based cohort of middle-age adults. We used genome-wide association (GWAS) data combined with clinical and biomarker information in the Dental Atherosclerosis Risk In Communities (ARIC) cohort. Genotypes comprised SNPs directly typed on the Affymetrix Genome-Wide Human SNP Array 6.0 chip with minor allele frequency of >5% (n = 656,292) or were imputed using HapMap II-CEU (n = 2,104,905). We investigated 30 traits including “global” [e.g., number of natural teeth (NT) and incident tooth loss], clinically defined (e.g., dental caries via the DMFS index, periodontitis via the CDC/AAP and WW17 classifications), and biologically informed (e.g., subgingival pathogen colonization and “complex” traits). Heritability (i.e., variance explained; h2) was calculated using Visscher’s Genome-wide Complex Trait Analysis (GCTA), using a random-effects mixed linear model and restricted maximum likelihood (REML) regression adjusting for ancestry (10 principal components), age, and sex. Heritability estimates were modest for clinical traits—NT = 0.11 (se = 0.07), severe chronic periodontitis (CDC/AAP) = 0.22 (se = 0.19), WW17 Stage 4 vs. 1/2 = 0.15 (se = 0.11). “High gingival index” and “high red complex colonization” had h2 > 0.50, while a periodontal complex trait defined by high IL-1β GCF expression and Aggregatibacter actinomycetemcomitans subgingival colonization had the highest h2 = 0.72 (se = 0.32). Our results indicate that all GWAS SNPs explain modest levels of the observed variance in clinical oral and dental measures. Subgingival bacterial colonization and complex phenotypes encompassing both bacterial colonization and local inflammatory response had the highest heritability, suggesting that these biologically informed traits capture aspects of the disease process and are promising targets for genomics investigations, according to the notion of precision oral health.



Drs. Divaris and Agler are supported by a grant from the National Institutes of Health/National Institute of Dental and Craniofacial Health Research (NIH/NIDCR) U01-DE025046. Dr. Marchesan is supported by K01-DE027087.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Cary S. Agler
    • 1
  • Kevin Moss
    • 1
  • Kamaira H. Philips
    • 1
  • Julie T. Marchesan
    • 2
  • Miguel Simancas-Pallares
    • 1
  • James D. Beck
    • 2
    • 3
  • Kimon Divaris
    • 3
    • 4
    Email author
  1. 1.Division of Oral and Craniofacial Health SciencesAdams School of Dentistry, University of North Carolina-Chapel HillChapel HillUSA
  2. 2.Division of Comprehensive Oral Health - PeriodontologyAdams School of Dentistry, University of North Carolina-Chapel HillChapel HillUSA
  3. 3.Department of EpidemiologyGillings School of Global Public Health, University of North Carolina-Chapel HillChapel HillUSA
  4. 4.Division of Pediatrics and Public HealthAdams School of Dentistry, University of North Carolina-Chapel HillChapel HillUSA

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