School of Dentistry, University of Leeds, Leeds, United Kingdom.
School of Medicine, University of Leeds, Leeds, United Kingdom.
PLoS One. 2024 Sep 6;19(9):e0306983. doi: 10.1371/journal.pone.0306983. eCollection 2024.
This study aims to systematically review the existing literature and critically appraise the evidence of genome-wide association studies (GWAS) on periodontitis. This study also aims to synthesise the findings of genetic risk variants of periodontitis from included GWAS.
A systematic search was conducted on PubMed, GWAS Catalog, MEDLINE, GLOBAL HEALTH and EMBASE via Ovid for GWAS on periodontitis. Only studies exploring single-nucleotide polymorphisms(SNPs) associated with periodontitis were eligible for inclusion. The quality of the GWAS was assessed using the Q-genie tool. Information such as study population, ethnicity, genomic data source, phenotypic characteristics(definition of periodontitis), and GWAS methods(quality control, analysis stages) were extracted. SNPs that reached conventional or suggestive GWAS significance level(5e-8 or 5e-06) were extracted and synthesized.
A total of 15 good-quality GWAS on periodontitis were included (Q-genie scores ranged from 38-50). There were huge heterogeneities among studies. There were 11 identified risk SNPs (rs242016, rs242014, rs10491972, rs242002, rs2978951, rs2738058, rs4284742, rs729876, rs149133391, rs1537415, rs12461706) at conventional GWAS significant level (p<5x10-8), and 41 at suggestive level (p<5x10-6), but no common SNPs were found between studies. Three SNPs (rs4284742 [G], rs11084095 [A], rs12461706 [T]) from three large studies were from the same gene region-SIGLEC5.
GWAS of periodontitis showed high heterogeneity of methodology used and provided limited SNPs statistics, making identifying reliable risk SNPs challenging. A clear guidance in dental research with requirement of expectation to make GWAS statistics available to other investigators are needed.
本研究旨在系统回顾现有文献，并批判性地评价牙周炎全基因组关联研究（GWAS）的证据。本研究还旨在综合纳入的 GWAS 中牙周炎遗传风险变异的研究结果。
通过 Ovid 在 PubMed、GWAS Catalog、MEDLINE、GLOBAL HEALTH 和 EMBASE 上进行了牙周炎 GWAS 的系统搜索。只有探索与牙周炎相关的单核苷酸多态性（SNP）的研究才符合纳入标准。使用 Q-genie 工具评估 GWAS 的质量。提取的信息包括研究人群、种族、基因组数据源、表型特征（牙周炎定义）和 GWAS 方法（质量控制、分析阶段）。提取并综合达到常规或提示性 GWAS 显著性水平（5e-8 或 5e-06）的 SNP。
共纳入 15 项高质量的牙周炎 GWAS（Q-genie 评分范围为 38-50）。研究之间存在很大的异质性。有 11 个确定的风险 SNP（rs242016、rs242014、rs10491972、rs242002、rs2978951、rs2738058、rs4284742、rs729876、rs149133391、rs1537415、rs12461706）达到常规 GWAS 显著水平（p<5x10-8），41 个达到提示性水平（p<5x10-6），但研究之间没有共同的 SNP。来自三项大型研究的三个 SNP（rs4284742[G]、rs11084095[A]、rs12461706[T]）来自同一个基因区域-SIGLEC5。
牙周炎的 GWAS 显示出所用方法学的高度异质性，并提供了有限的 SNP 统计数据，使得识别可靠的风险 SNP 具有挑战性。需要在牙科研究中提供明确的指导，并要求将 GWAS 统计数据提供给其他研究人员。
