Department of Periodontology and Synoptic Dentistry, Institute of Health, Institute for Dental and Craniofacial Sciences, Charité-University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Institute for Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany.
Eur J Hum Genet. 2019 Jan;27(1):102-113. doi: 10.1038/s41431-018-0265-5. Epub 2018 Sep 14.
Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10, OR = 1.36, 95% CI = [1.23-1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10, OR = 1.24, 95% CI = [1.15-1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.
牙周炎是最常见的炎症性疾病之一，在全球范围内，严重形式的患病率为 11%，估计遗传率为 50%。它分为广泛的中度慢性牙周炎 (CP) 和罕见的早发性和严重表型侵袭性牙周炎 (AgP)。这些不同的疾病表现被认为具有共同的风险等位基因和易患的环境因素。为了深入了解这两种形式的共同遗传病因和潜在的分子机制，我们使用两种表型的全基因组关联研究进行了两步式荟萃分析方法。纳入了来自 AgP 和 CP 全基因组关联研究 (GWAS) 的基因型，这些研究包括具有北欧遗传背景的 5095 例病例和 9908 例对照。两个位于染色体 8 上的假基因 MTND1P5 内的基因座 (rs16870060-G，P = 3.69 × 10，OR = 1.36，95%CI = [1.23-1.51]) 和染色体 16 上长基因间非编码 RNA LOC107984137 的内含子内的位点与牙周炎在全基因组显著性水平相关(rs729876-T，P = 9.77 × 10，OR = 1.24，95%CI = [1.15-1.34])。这项研究确定了牙周炎的新风险基因座，增加了 AgP 和 CP 的遗传基础。
