Journal
HUMAN MOLECULAR GENETICS
Volume 22, Issue 11, Pages 2312-2324Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt065
Keywords
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Funding
- National Heart, Lung, and Blood Institute [HHSN268201100 005C, HHSN268201100006C, HHSN268201100007C, HHSN 268201100008C, HHSN268201100009C, HHSN26820110 0010C, HHSN268201100011C, HSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN2682006252 26C, N01AG6210, R01HL74104]
- National Institute of Environmental Health Sciences [P30ES010126]
- National Institute of Dental and Craniofacial Research [R01DE11551, R01DE021418]
- National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]
- NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]
- Center for Inherited Disease Research (CIDR)
- The Johns Hopkins University [HHSN268200782096C]
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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 ageu62 years, moderate CPu43 and severe CPu17). 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)uNPY, rs2521634 [G]: odds ratio [OR 1.49 (95 confidence interval (CI 1.281.73, P 3.5 10(7)))]; moderate CP (n 2293)uNCR2, rs7762544 [G]: OR 1.40 (95 CI 1.241.59, P 7.5 10(8)), EMR1, rs3826782 [A]: OR 2.01 (95 CI 1.522.65, 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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