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Exploring the Genetic Basis of Chronic Periodontitis: A Genome-Wide Association Study

Citation

Divaris, Kimon; Monda, Keri L.; North, Kari E.; Olshan, Andrew F.; Reynolds, Lindsay M.; Hsueh, Wen-Chi; Lange, Ethan M.; Moss, Kevin; Barros, Silvana P.; & Weyant, Robert J., et al. (2013). Exploring the Genetic Basis of Chronic Periodontitis: A Genome-Wide Association Study. Human Molecular Genetics, 22(11), 2312-2324. PMCID: PMC3652417

Abstract

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.

URL

http://dx.doi.org/10.1093/hmg/ddt065

Reference Type

Journal Article

Year Published

2013

Journal Title

Human Molecular Genetics

Author(s)

Divaris, Kimon
Monda, Keri L.
North, Kari E.
Olshan, Andrew F.
Reynolds, Lindsay M.
Hsueh, Wen-Chi
Lange, Ethan M.
Moss, Kevin
Barros, Silvana P.
Weyant, Robert J.
Liu, Yongmei
Newman, Anne B.
Beck, James D.
Offenbacher, Steven

PMCID

PMC3652417