Replication of gene polymorphisms associated with periodontitis-related traits in an elderly cohort: the Washington Heights/Inwood Community Aging Project Ancillary Study of Oral Health

J Clin Periodontol. 2022 May;49(5):414-427. doi: 10.1111/jcpe.13605. Epub 2022 Mar 16.


Aim: We sought to replicate findings from published genome-wide association studies (GWAS), linking specific candidate gene loci with periodontitis-related clinical/microbial traits.

Materials and methods: In the published GWAS, a total of 2196 single nucleotide polymorphisms associated with periodontitis-related traits at a p ≤ 5 × 10-6 and mapped to 136 gene loci. The replication cohort included 1124 individuals, 65-98 years old (67% female, 45% Hispanic, 30% Black, 23% White) with available genome-wide genotypes and full-mouth periodontal status. Microbial profiles using checkerboard DNA-DNA hybridization and 16SrRNA sequencing were available from 912 and 739 participants, respectively.

Results: Using gene-specific p-values after linkage disequilibrium pruning, the following gene/phenotype associations replicated successfully: CLEC19A with edentulism and %teeth with pocket depth (PD) ≥4 mm; IL37, HPVC1, TRPS1, ABHD12B, LDLRAD4 (C180rF1), TGM3, and GRK5 with %teeth with PD ≥4 mm; DAB2IP with presence of PD ≥6 mm; KIAA1715(LNPK), ROBO2, RAB28, LINC01017, NELL1, LDLRAD4(C18orF1), and CRYBB2P1 with %teeth with clinical attachment level (CAL) ≥3 mm; RUNX2 and LAMA2 with %teeth with CAL ≥5 mm; and KIAA1715(LNPK) with high colonization by Aggregatibacter actinomycetemcomitans. In addition, CLEC19A, IQSEC1, and EMR1 associated with microbial abundance based on checkerboard data, LBP and NCR2 with abundance based on sequencing data, and NCR2 with microbial diversity based on sequencing data.

Conclusions: Several gene loci identified in published GWAS as associated with periodontitis-related phenotypes replicated successfully in an elderly cohort.

Keywords: epidemiology; genome-wide association study; multi-ethnic; periodontal disease; replication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aging
  • Chronic Periodontitis* / genetics
  • DNA
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Interleukin-1
  • Male
  • Oral Health
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Repressor Proteins / genetics
  • Transglutaminases / genetics
  • Washington
  • rab GTP-Binding Proteins
  • ras GTPase-Activating Proteins / genetics


  • DAB2IP protein, human
  • IL37 protein, human
  • Interleukin-1
  • Repressor Proteins
  • TRPS1 protein, human
  • ras GTPase-Activating Proteins
  • DNA
  • TGM3 protein, human
  • Transglutaminases
  • RAB28 protein, human
  • rab GTP-Binding Proteins