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，牙齿疾病与全身之间存在双向关系 糖尿病和心血管疾病（CVD）等疾病，其慢性炎症状态由 牙齿感染归因于系统性疾病发病机理的合理因素。尽管有研究 进展，这些研究的结果是有争议的。在阻碍进步的阻碍因素中 领域是缺乏综合的牙科，医学和基因组数据，因此有关 有助于牙科和全身性疾病关系的宿主生物学机制。在以前的研究中，我们 已经显示了结合遗传和流行病学结合分析以推进的重要性 关于牙科和全身性疾病关系的知识。此外，我们已经表明了牙科疾病的变化 相关的局部局部与30个全身性疾病的风险增加显着相关。在这个 应用，我们将检验以下假设，即潜在的共同遗传病因可能有助于 牙齿和全身性疾病与建议之间的相互联系，一项大规模研究与综合 参与者数据以获取更确定的发现并将领域推向前进。我们将利用和整合高 质量临床（牙科和医学），基因组和人口统计数据可从20万名参与者获得 我们所有的研究计划，以确定最有可能导致牙齿 +组合表型的宿主因素 全身性疾病。我们将确定与每个组合表型相关的基因变体，并确定 多基因风险是否会增加对植物组合的风险。这项研究代表了重大进展 通过创建一个路线图，以将临床和基因组数据从大而多样化的人群整合到 阐明宿主易于诱发因素对牙科 +全身性疾病表型的贡献。生成的数据 通过该建议将在我们所有的研究人员工作台中提供。该提案解决了NIDCR的 战略优先级＃1整合口头和一般健康，以及＃2精密牙科医学。