Leveraging All of Us data to unravel the interconnectedness between dental and systemic disease

项目总结 流行病学研究表明，牙科疾病和系统性疾病之间存在双向关系。 糖尿病和心血管疾病(CVD)等疾病，慢性炎症状态由 牙齿感染被认为是全身性疾病发病的一个看似合理的促成因素。尽管有研究 随着研究的进展，这些研究的结果存在争议。在阻碍取得进展的因素中， 该领域缺乏完整的牙科、医学和基因组数据，因此留下了许多关于 促进牙科和全身疾病关系的宿主生物学机制。在之前的研究中，我们 已经表明了结合遗传和流行病学关联分析的重要性，以推动 了解牙科和全身疾病之间的关系。此外，我们已经证明了牙病的变异 相关基因座显著增加了患系统性疾病的风险。在这 应用，我们将检验一个假设，即潜在的共同遗传病因学可能有助于 牙科和全身疾病之间的相互联系，并建议进行一项大规模研究，将 参与者数据，以获得更具结论性的结论，并推动这一领域向前发展。我们将利用和整合高- 高质量的临床(牙科和医学)、基因组和人口学数据来自&gt；200,000名参与者。 我们所有人的研究计划，以确定最有可能导致牙科+的联合表型的宿主因素 系统性疾病。我们将识别与每种组合表型相关的基因变异，并确定 多基因风险是否会增加合并表型的风险。这项研究代表着以下方面的重大进展 通过创建路线图，将来自大量不同人群的临床和基因组数据整合到 阐明宿主易感因素对牙科+全身疾病表型的影响。生成的数据 通过这项提议将在我们所有的研究人员工作台上可用。该提案涉及NIDCR的 战略优先事项#1整合口腔和一般健康，#2精密牙科医学。

PROJECT SUMMARY Epidemiological studies have suggested a bidirectional relationship between dental disease and systemic conditions such as diabetes and cardiovascular disease (CVD), with the chronic inflammatory state caused by dental infections attributed as a plausible contributing factor to systemic disease pathogenesis. Despite research progress, the results of these studies are controversial. Among the hindering factors impeding progress in the field is the lack of integrated dental, medical, and genomic data thereby leaving much to be learned about the host biological mechanisms contributing to dental and systemic disease relationships. In previous studies, we have shown the importance of combining genetic and epidemiological association analysis to advance knowledge on dental and systemic disease relationships. Further, we’ve shown that variation in dental-disease associated loci were significantly associated with increased risk for >30 systemic disease phecodes. In this application, we will test the hypothesis that a potential shared genetic etiology may contribute to the interconnectedness between dental and systemic disease and propose a large-scale study with integrated participant data for more conclusive findings and to move the field forward. We will leverage and integrate high- quality clinical (dental and medical), genomic, and demographic data available from >200,000 participants in the All of Us Research Program to identify host factors most likely contributing to a combined phenotype of dental + systemic disease. We will identify gene variants associated with each combined phenotype and determine whether polygenic risk can increase risk to a combined phentoype. This study represents a major advance in the field by creating a roadmap for integrating clinical and genomic data from a large and diverse population to elucidate the contributions of host predisposing factors to dental + systemic disease phenotypes. Data generated through this proposal will be available in the All of Us Researcher Workbench. This proposal addresses NIDCR’s Strategic Priorities #1 Integrate Oral and General Health, and #2 Precision Dental Medicine.