Abstract：
Few genome-wide association studies (GWAS) have been conducted for severe forms of periodontitis (stage III/IV grade C), and the number of known risk genes is scarce. To identify further genetic risk variants to improve the understanding of the disease aetiology, a GWAS meta-analysis in cases with a diagnosis at ≤35 years of age was performed.
Genotypes from German, Dutch and Spanish GWAS studies of III/IV-C periodontitis diagnosed at age ≤35 years were imputed using TopMed. After quality control, a meta-analysis was conducted on 8,666,460 variants in 1306 cases and 7817 controls with METAL. Variants were prioritized using FUMA for gene-based tests, functional annotation and a transcriptome-wide association study integrating eQTL data.
The study identified a novel genome-wide significant association in the FCER1G gene (p = 1.0 × 10-9 ), which was previously suggestively associated with III/IV-C periodontitis. Six additional genes showed suggestive association with p < 10-5 , including the known risk gene SIGLEC5. HMCN2 showed the second strongest association in this study (p = 6.1 × 10-8 ).
This study expands the set of known genetic loci for severe periodontitis with an age of onset ≤35 years. The putative functions ascribed to the associated genes highlight the significance of oral barrier tissue stability, wound healing and tissue regeneration in the aetiology of these periodontitis forms and suggest the importance of tissue regeneration in maintaining oral health.
Genotypes from German, Dutch and Spanish GWAS studies of III/IV-C periodontitis diagnosed at age ≤35 years were imputed using TopMed. After quality control, a meta-analysis was conducted on 8,666,460 variants in 1306 cases and 7817 controls with METAL. Variants were prioritized using FUMA for gene-based tests, functional annotation and a transcriptome-wide association study integrating eQTL data.
The study identified a novel genome-wide significant association in the FCER1G gene (p = 1.0 × 10-9 ), which was previously suggestively associated with III/IV-C periodontitis. Six additional genes showed suggestive association with p < 10-5 , including the known risk gene SIGLEC5. HMCN2 showed the second strongest association in this study (p = 6.1 × 10-8 ).
This study expands the set of known genetic loci for severe periodontitis with an age of onset ≤35 years. The putative functions ascribed to the associated genes highlight the significance of oral barrier tissue stability, wound healing and tissue regeneration in the aetiology of these periodontitis forms and suggest the importance of tissue regeneration in maintaining oral health.
摘要：
目的：对严重形式的牙周炎（III/IV级C）进行了很少的全基因组关联研究（GWAS），已知的风险基因数量很少。为了进一步确定遗传风险变异，以提高对疾病病因的理解，对诊断为≤35岁的病例进行了GWAS荟萃分析.
方法：来自德国的基因型，使用TopMed估算了荷兰和西班牙对年龄≤35岁的III/IV-C牙周炎的GWAS研究。质量控制后,采用METAL对1306例病例和7817例对照的8,666,460个变异体进行了荟萃分析.变体使用FUMA进行基于基因的测试，功能注释和整合eQTL数据的全转录组关联研究。
结果：该研究在FCER1G基因（p=1.0×10-9）中发现了一种新的全基因组显著关联，以前暗示与III/IV-C牙周炎有关。另外六个基因显示出p<10-5的暗示性关联，包括已知的风险基因SIGLEC5。HMCN2在本研究中表现出第二强的相关性(p=6.1×10-8)。
结论：本研究扩展了发病年龄≤35岁的重度牙周炎的已知遗传基因座组。归因于相关基因的推定功能突出了口腔屏障组织稳定性的重要性，这些牙周炎形成的病因学中的伤口愈合和组织再生，并表明组织再生在维持口腔健康中的重要性。
方法：来自德国的基因型，使用TopMed估算了荷兰和西班牙对年龄≤35岁的III/IV-C牙周炎的GWAS研究。质量控制后,采用METAL对1306例病例和7817例对照的8,666,460个变异体进行了荟萃分析.变体使用FUMA进行基于基因的测试，功能注释和整合eQTL数据的全转录组关联研究。
结果：该研究在FCER1G基因（p=1.0×10-9）中发现了一种新的全基因组显著关联，以前暗示与III/IV-C牙周炎有关。另外六个基因显示出p<10-5的暗示性关联，包括已知的风险基因SIGLEC5。HMCN2在本研究中表现出第二强的相关性(p=6.1×10-8)。
结论：本研究扩展了发病年龄≤35岁的重度牙周炎的已知遗传基因座组。归因于相关基因的推定功能突出了口腔屏障组织稳定性的重要性，这些牙周炎形成的病因学中的伤口愈合和组织再生，并表明组织再生在维持口腔健康中的重要性。
