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

利用我们所有人的数据来揭示牙科和全身疾病之间的相互关联

• 批准号: 10798866
• 负责人: Ariadne M Letra
• 金额: $ 15.9万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10798866
• 关键词: Address; All of Us Research Program; Animals; Biological; Birth; Cardiovascular Diseases; Chronic; Clinical; Clinical Data; Coronary Arteriosclerosis; Data; Data Set; Dental; Dental Records; Dental caries; Diabetes Mellitus; Disease; Epidemiology; Future; Genes; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genomics; Genotype; Goals; Health; Hypertension; Individual; Inflammatory; Integration Host Factors; Knowledge; Learning; Medical; Medical Records; Medicine; Modeling; National Institute of Dental and Craniofacial Research; Oral; Oral health; Participant; Pathogenesis; Pathway interactions; Patients; Periapical Diseases; Periapical Periodontitis; Pharmaceutical Preparations; Phenotype; Population; Population Group; Population Heterogeneity; Precipitating Factors; Predisposing Factor; Predisposition; Research; Research Personnel; Risk; Statistical Methods; Surveys; Systemic disease; Testing; Tooth Diseases; Variant; dental infection; disease phenotype; dysbiosis; environmental stressor; epidemiology study; genetic architecture; genetic variant; genome-wide; genomic data; health care availability; improved; microbial; novel; phenome; polygenic risk score; population stratification; programs; risk variant; sex; social health determinants; tool

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.

项目摘要 流行病学研究表明，牙齿疾病和全身性疾病之间存在双向关系。 疾病如糖尿病和心血管疾病（CVD），伴随着慢性炎症状态， 牙齿感染被认为是全身性疾病发病机制的合理因素。尽管研究 这些研究的结果是有争议的。在阻碍发展方面取得进展的障碍因素中， 该领域缺乏综合的牙科，医疗和基因组数据，从而留下了很多关于 宿主的生物学机制有助于牙齿和全身疾病的关系。在以前的研究中，我们 已经表明了结合遗传和流行病学关联分析的重要性， 了解牙科和全身疾病的关系。此外，我们还发现， 相关基因座与>30个系统性疾病phecodes的风险增加显著相关。在这 应用程序，我们将测试的假设，一个潜在的共同遗传病因可能有助于 牙科和全身性疾病之间相互联系，并建议进行一项大规模研究， 与会者的数据，以更确凿的调查结果，并推动该领域向前发展。我们将利用和整合高- 高质量的临床（牙科和医疗），基因组和人口统计数据，可从> 200，000参与者中获得， 我们所有的研究计划，以确定最有可能导致牙科+ 全身性疾病。我们将鉴定与每种组合表型相关的基因变异， 多基因风险是否会增加合并表型的风险。这项研究代表了一个重大进展， 通过创建一个路线图，整合来自大量不同人群的临床和基因组数据， 阐明宿主易感因素对牙科+全身性疾病表型的贡献。生成的数据 将在All of Us Researcher中提供。该提案涉及NIDCR的 战略优先事项#1整合口腔和一般健康，#2精准牙科医学。