Gao Chenyi, Iles Mark M, Bishop David Timothy, Larvin Harriet, Bunce David, Wu Bei, Luo Huabin, Nibali Luigi, Pavitt Susan, Wu Jianhua, Kang Jing
Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
School of Dentistry, University of Leeds, Leeds, UK.
Clin Oral Investig. 2025 Feb 14;29(2):129. doi: 10.1007/s00784-025-06205-8.
Periodontitis is linked with many health conditions, but its genetic basis is not yet understood. This genome-wide association study (GWAS) aimed to investigate the genetic variants associated with periodontitis.
This study utilised UK Biobank participants of European descent. Individuals were categorised as "having periodontitis" if they self-reported having 'painful gums', 'bleeding gums' or 'loose teeth' (n = 68,482), or as "controls" for those without these symptoms (n = 307,342). We conducted GWAS of this binary periodontitis phenotype using logistic regression models with PLINK2.0 adjusting for age, sex and the first 15 principal components to account for population stratification.
There were 376,611 participants (mean baseline age = 57 ± 7.9 SD) included in the GWAS, and four significant loci were identified: rs775476621 on chromosome 11 (Odds Ratio, OR[T]: 3.08, p = 1.01 × 10), rs751014048 on chromosome 11 (OR[G]: 3.07, p = 1.04 × 10), rs149922301 on chromosome 4 near gene RP11-61G19.1 (OR[A]: 1.18, p = 2.71 × 10) and rs368467810 on chromosome 6 near gene HIST1H3L (OR[TTTA]: 0.96, p = 3.88 × 10).
Within the current limitations, such as self-reported phenotype and older age of the study population, four loci were detected for periodontitis that have not previously been linked with this condition. Further exploration of the function of these loci may contribute to improved understanding of periodontitis aetiology and subsequent drug development.
These findings offer new targets for future research to investigate the genetic impact on periodontitis and aid the future understanding of periodontitis pathology and the disease's progression.
牙周炎与多种健康状况相关，但其遗传基础尚未明确。这项全基因组关联研究（GWAS）旨在调查与牙周炎相关的基因变异。
本研究使用了英国生物银行中欧洲血统的参与者。如果个体自我报告有“牙龈疼痛”“牙龈出血”或“牙齿松动”，则被归类为“患有牙周炎”（n = 68,482），而没有这些症状的个体则作为“对照”（n = 307,342）。我们使用PLINK2.0软件，通过逻辑回归模型对这种二元牙周炎表型进行GWAS分析，并对年龄、性别和前15个主成分进行调整，以考虑人群分层。
GWAS纳入了376,611名参与者（平均基线年龄 = 57 ± 7.9标准差），并确定了四个显著位点：11号染色体上的rs775476621（优势比，OR[T]：3.08，p = 1.01 × 10），11号染色体上的rs751014048（OR[G]：3.07，p = 1.04 × 10），4号染色体上靠近基因RP11 - 61G19.1的rs149922301（OR[A]：1.18，p = 2.71 × 10）以及6号染色体上靠近基因HIST1H3L的rs368467810（OR[TTTA]：0.96，p = 3.88 × 10）。
在当前的局限性（如自我报告的表型和研究人群年龄较大）下，检测到了四个与牙周炎相关的位点，这些位点此前未与该疾病相关联。对这些位点功能的进一步探索可能有助于加深对牙周炎病因的理解以及后续药物研发。
这些发现为未来研究提供了新的靶点，以调查遗传因素对牙周炎的影响，并有助于未来对牙周炎病理及疾病进展的理解。
