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Exploring the genetic basis of chronic periodontitis: a genome-wide association study.

Publication ,  Journal Article
Divaris, K; Monda, KL; North, KE; Olshan, AF; Reynolds, LM; Hsueh, W-C; Lange, EM; Moss, K; Barros, SP; Weyant, RJ; Liu, Y; Newman, AB ...
Published in: Hum Mol Genet
June 1, 2013

Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age-62 years, moderate CP-43% and severe CP-17%). We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 × 10(-6)) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP. Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study. Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)-NPY, rs2521634 [G]: odds ratio [OR = 1.49 (95% confidence interval (CI = 1.28-1.73, P = 3.5 × 10(-7)))]; moderate CP (n = 2293)-NCR2, rs7762544 [G]: OR = 1.40 (95% CI = 1.24-1.59, P = 7.5 × 10(-8)), EMR1, rs3826782 [A]: OR = 2.01 (95% CI = 1.52-2.65, P = 8.2 × 10(-7)). Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways. A significant interaction of NUAK1 (rs11112872, interaction P = 2.9 × 10(-9)) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking. These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

June 1, 2013

Volume

22

Issue

11

Start / End Page

2312 / 2324

Location

England

Related Subject Headings

  • Signal Transduction
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
 

Citation

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Divaris, K., Monda, K. L., North, K. E., Olshan, A. F., Reynolds, L. M., Hsueh, W.-C., … Offenbacher, S. (2013). Exploring the genetic basis of chronic periodontitis: a genome-wide association study. Hum Mol Genet, 22(11), 2312–2324. https://doi.org/10.1093/hmg/ddt065
Divaris, Kimon, Keri L. Monda, Kari E. North, Andrew F. Olshan, Lindsay M. Reynolds, Wen-Chi Hsueh, Ethan M. Lange, et al. “Exploring the genetic basis of chronic periodontitis: a genome-wide association study.Hum Mol Genet 22, no. 11 (June 1, 2013): 2312–24. https://doi.org/10.1093/hmg/ddt065.
Divaris K, Monda KL, North KE, Olshan AF, Reynolds LM, Hsueh W-C, et al. Exploring the genetic basis of chronic periodontitis: a genome-wide association study. Hum Mol Genet. 2013 Jun 1;22(11):2312–24.
Divaris, Kimon, et al. “Exploring the genetic basis of chronic periodontitis: a genome-wide association study.Hum Mol Genet, vol. 22, no. 11, June 2013, pp. 2312–24. Pubmed, doi:10.1093/hmg/ddt065.
Divaris K, Monda KL, North KE, Olshan AF, Reynolds LM, Hsueh W-C, Lange EM, Moss K, Barros SP, Weyant RJ, Liu Y, Newman AB, Beck JD, Offenbacher S. Exploring the genetic basis of chronic periodontitis: a genome-wide association study. Hum Mol Genet. 2013 Jun 1;22(11):2312–2324.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

June 1, 2013

Volume

22

Issue

11

Start / End Page

2312 / 2324

Location

England

Related Subject Headings

  • Signal Transduction
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study