Polygenic Risk Modelling in Periodontitis: Insights From a Feasibility Study of 4243 European Cases and Current Limitations.

IF 8.3 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Clinical Periodontology Pub Date : 2026-08-21 DOI:10.1111/jcpe.70195

Gesa M Richter, O Mercy Akinloye, M Kamal Nasr, Birte Holtfreter, Alicia de Coo, Silvia Diz De Almeida, Bruno G Loos, Søren Jepsen, Henrik Dommisch, Corinna Bruckmann, Ines Kapferer-Seebacher, Georg Homuth, Thomas Kocher, Henry Völzke, Klaus Berger, Matthias Laudes, Wolfgang Lieb, Nathalie van der Velde, Natasja van Schoor, Lisette de Groot, Juan Blanco, Angel Carracedo, Raquel Cruz, Astrid Dempfle, Alexander Teumer, Arne S Schaefer, Sandra Freitag-Wolf

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引用次数: 0

Abstract

Background and aim: Genetic susceptibility plays a particularly important role in early-onset (EO) and severe periodontitis (PD). The genetic risk remains largely unexplained because of limited sample sizes and heterogeneous phenotypes in genome-wide association studies (GWAS). This study investigates whether current GWAS data can be used to construct a polygenic score (PGS) capturing genetic susceptibility to severe PD.

Materials and methods: A PGS was developed in a three-step design, using a German EO-III/IV-C-PD GWAS (n = 692 cases, ≤ 35 years at diagnosis) as the base dataset, a Spanish EO-III/IV-C-PD GWAS (n = 441 cases) to optimise the score, and as validation a Dutch EO-III/IV-C-PD GWAS (n = 171 cases) and a German population-based GWAS with later-onset III/IV-PD (Studies of Health in Pomerania [SHIP], n = 2941 cases).

Results: The PGS showed a trend towards association with disease status in the Spanish sample (Nagelkerke R² = 0.4%, p = 0.06; AUC = 0.52; 95% confidence interval [CI]: 0.49-0.56), but not in the smaller Dutch dataset (R² = 0.2%, p = 0.18; AUC = 0.52; 95% CI: 0.48-0.57) or in the SHIP dataset (AUC = 0.50, 95% CI: 0.48-0.52). Case-control distributions overlapped substantially. Genetic correlation analyses revealed no strong overlap with other associated traits.

Conclusions: Current PGS models have limited case-control discriminative ability for PD. Larger harmonised studies are needed to enhance genetic risk prediction and clarify pleiotropic relationships.

查看原文本刊更多论文

牙周炎的多基因风险模型：来自4243例欧洲病例的可行性研究和当前局限性的见解。

背景与目的：遗传易感性在早发性（EO）和重度牙周炎（PD）中起着特别重要的作用。由于全基因组关联研究（GWAS）的样本量有限和异质性表型，遗传风险在很大程度上仍然无法解释。本研究探讨了当前的GWAS数据是否可以用于构建捕获严重帕金森病遗传易感性的多基因评分（PGS）。材料与方法:一个后卫是在三步设计开发的,使用德国EO-III / IV-C-PD GWAS (n = 692例,诊断≤35年)为基础数据集,一个西班牙EO-III / IV-C-PD GWAS (n = 441例)优化得分,以及验证荷兰EO-III / IV-C-PD GWAS (n = 171例)和德国以人群为基础的GWAS later-onset III / IV-PD(卫生研究波美拉尼亚(船),n = 2941例)。结果：PGS在西班牙样本中显示出与疾病状态相关的趋势（Nagelkerke R2 = 0.4%, p = 0.06; AUC = 0.52； 95%可信区间[CI]: 0.49-0.56），但在较小的荷兰数据集（R2 = 0.2%, p = 0.18; AUC = 0.52; 95% CI: 0.48-0.57）或SHIP数据集（AUC = 0.50, 95% CI: 0.48-0.52）中没有这种趋势。病例-对照分布有很大重叠。遗传相关分析显示与其他相关性状无明显重叠。结论：目前的PGS模型对PD的病例对照判别能力有限。需要更大规模的协调研究来加强遗传风险预测和澄清多效性关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Periodontology 医学-牙科与口腔外科

CiteScore

13.30

自引率

10.40%

发文量

175

审稿时长

3-8 weeks

期刊介绍： Journal of Clinical Periodontology was founded by the British, Dutch, French, German, Scandinavian, and Swiss Societies of Periodontology. The aim of the Journal of Clinical Periodontology is to provide the platform for exchange of scientific and clinical progress in the field of Periodontology and allied disciplines, and to do so at the highest possible level. The Journal also aims to facilitate the application of new scientific knowledge to the daily practice of the concerned disciplines and addresses both practicing clinicians and academics. The Journal is the official publication of the European Federation of Periodontology but wishes to retain its international scope. The Journal publishes original contributions of high scientific merit in the fields of periodontology and implant dentistry. Its scope encompasses the physiology and pathology of the periodontium, the tissue integration of dental implants, the biology and the modulation of periodontal and alveolar bone healing and regeneration, diagnosis, epidemiology, prevention and therapy of periodontal disease, the clinical aspects of tooth replacement with dental implants, and the comprehensive rehabilitation of the periodontal patient. Review articles by experts on new developments in basic and applied periodontal science and associated dental disciplines, advances in periodontal or implant techniques and procedures, and case reports which illustrate important new information are also welcome.