Department of Pediatric Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
Hum Mol Genet. 2013 Jun 1;22(11):2312-24. doi: 10.1093/hmg/ddt065. Epub 2013 Mar 4.
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.
慢性牙周炎（CP）是一种常见的口腔疾病，会带来大量的系统性炎症和微生物负担，是牙齿脱落的主要原因。在这里，我们展示了一项在参加动脉粥样硬化风险社区（ARIC）研究的 4504 名欧洲裔美国人（EA）队列中进行的 CP 全基因组关联研究的结果（平均年龄 62 岁，中度 CP-43%，重度 CP-17%）。我们没有发现 CP 的全基因组显著关联信号；然而，我们发现了六个位点的关联信号（P < 5 × 10(-6)），包括严重 CP 的 NIN、NPY、WNT5A 和中度 CP 的 NCR2、EMR1、10p15。这三个位点在健康、衰老和身体成分（健康 ABC）研究中 656 名成年 EA 参与者的独立样本中具有一致的效应大小和方向。Meta 分析汇总估计为严重 CP（n = 958 与健康：n = 1909）-NPY，rs2521634[G]：比值比[OR = 1.49（95%置信区间（CI = 1.28-1.73，P = 3.5 × 10(-7)))]；中度 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))）。经典途径分析表明，神经系统信号、细胞免疫反应和细胞因子信号途径显著富集。ARIC 中 NUAK1（rs11112872，交互 P = 2.9 × 10(-9)）与吸烟的显著相互作用在健康 ABC 中未得到复制，尽管 CP 中所有单核苷酸多态性解释的遗传方差估计值从 18%增加到 52%，但纳入与吸烟的全基因组相互作用项。这些全基因组关联研究结果为 CP 的进一步遗传研究提供了多个候选区域和途径的信息。
