Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci
Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci
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DOI：
10.1038/s41431-018-0265-5
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发表时间：
2019-01-01
影响因子：
5.2
通讯作者：
Schaefer, Arne S.
中科院分区：
文献类型：
--
作者：
Munz, Matthias;Richter, Gesa M.;Schaefer, Arne S.
牙周炎是最常见的炎症性疾病之一，全球范围内重度牙周炎的患病率为 11%，估计遗传率为 50%。它分为广泛的中度慢性牙周炎（CP）和罕见的早发性重度表型侵袭性牙周炎（AgP）。这些不同的疾病表现被认为具有相同的风险等位基因和诱发环境因素。为了获得对两种形式的共同遗传病因和潜在分子机制的新见解，我们利用两种表型的全基因组关联研究进行了两步荟萃分析方法。包括来自 AgP 和 CP 的估算全基因组关联研究 (GWAS) 的基因型，其中包括 5,095 例病例和 9,908 例西北欧遗传背景对照。两个基因座在全基因组显着性水平上与牙周炎相关。它们位于 8 号染色体上的假基因 MTND1P5（rs16870060-G，P = 3.69 x 10(-9)，OR= 1.36，95% CI = [1.23-1.51]）内，以及 16 号染色体上的长基因间非编码 RNA LOC107984137 的内含子内，基因 SHISA9 的下游（rs729876-T，P = 9.77 x 10(-9)，OR = 1.24，95% CI = [1.15-1.34]）。这项研究确定了牙周炎的新风险位点，增加了 AgP 和 CP 的遗传基础。
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 x 10(-9), 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 x 10(-9), 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.