Modeling childhood dental caries patterns for genomic and epigenetic analysis

为基因组和表观遗传分析建立儿童龋齿模式模型

• 批准号: 8984300
• 负责人: John R Shaffer
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8984300
• 关键词: Academy; Affect; American; Animal Model; Appalachian Region; Asthma; Behavioral Genetics; Child; Childhood; Chromosome Mapping; Chronic Disease; Cluster Analysis; Comorbidity; Complex; Data; Dental Care; Dental Enamel; Dental caries; Dentition; Development; Disadvantaged; Disease; Early Intervention; Eating; Endogenous Factors; Environment; Environmental Risk Factor; Epigenetic Process; Expenditure; Failure to Thrive; Family Study; Fluorides; Future; Genes; Genetic; Genetic Risk; Genetic study; Genome; Genomics; Genotype; Hay fever; Health; Health Care Costs; Hearing; Heritability; Immune response; Inherited; Intervention; Iowa; Knowledge; Lead; Lesion; Life; Measures; Meta-Analysis; Methods; Modeling; Morphology; National Institute of Dental and Craniofacial Research; Operative Surgical Procedures; Oral health; Other Genetics; Parents; Patients; Pattern; Pediatrics; Performance; Phenotype; Philosophy; Plant Roots; Positioning Attribute; Predisposition; Prevalence; Preventive measure; Primary Dentition; Public Health; Public Policy; Quality of life; Research; Resources; Risk; Risk Assessment; Risk Factors; Rural; Sampling; Schools; Self Perception; Sleep; Statistical Methods; Surface; Time; Tooth Loss; Tooth structure; Twin Multiple Birth; United States; Validation; Variant; Vision; aged; base; chronic pain; cohort; cost; demographics; disorder later incidence prevention; disorder prevention; experience; genetic analysis; genetic risk factor; genetic variant; genome wide association study; health disparity; high risk; improved; innovation; novel; personalized management; personalized medicine; prevent; response; restoration; saliva composition; social; socioeconomics; suburb; success; symptom treatment; tooth surface

DESCRIPTION (provided by applicant): Dental caries is the most common chronic disease in US children, and has actually increased in prevalence among young children in the last decade. Untreated childhood dental caries has a profound negative impact on quality of life, leading to many serious comorbidities, including chronic pain, tooth loss, difficulty hearing, eating, and sleeping, and failure to thrive, as well as poor school performance, social relationships, and self image, and decreased success later in life. In response to these negative health and social consequences, dental caries has become a focal issue in efforts to reduce public health disparities for both the NIDCR and the American Academy of Pediatrics. Treatment of dental caries consumes over $50 billion annually in dental health care costs; however, these expenditures are unfortunately concentrated in a caries management paradigm of surgical restoration (or extraction), which treats the symptoms of dental caries, while ignoring the root causes of disease. This approach disadvantages those with socioeconomic, geographic, or logistical barriers to accessing routine dental care. In order to shift the caries management paradigm to a model of risk assessment, early intervention, and recurrence prevention, the etiological factors controlling caries susceptibility will need to be identified. Our project seeksto fill this need, focusing on the genetic factors contributing to disease and applying innovative statistical methods of modeling dental caries experience. Indeed, studies shown that up to 60% of variation in caries experience may be attributed to host genetics; however, little is presently known about the specific genetic variants that contribute to cariogenesis, how these genes interact with environmental risk factors, and whether inherited epigenetic factors are also involved. This proposal will seek to fill the gap in knowledge regarding the environmental and genetic factors leading to childhood dental caries by modeling the patterns of caries across the dentition. We will conduct genome-wide association analysis utilizing two existing samples totaling 1,500 children aged 3 to 12 years with quality caries and risk factor assessments and available genotype data from a high-throughput microarray platform. We hypothesize that the effects exerted by risk factors lead to patterns of decay, which can be modeled, and in turn used for identifying and characterizing the environmental, genetic, and epigenetic factors involved. Understanding the complex interplay between genetic and environmental contributors to dental caries may lead to never-before-considered targets for intervention, heralding the era of personalized medicine where dental caries management will be tailored to a patient's specific suite of genetic and environmental liabilities. The potential gains of this project are enormous and come at minimal costs.

描述（由申请人提供）：龋齿是美国儿童中最常见的慢性疾病，在过去十年中，龋齿在幼儿中的患病率实际上有所增加。儿童龋齿未经治疗会对生活质量产生深远的负面影响，导致许多严重的合并症，包括慢性疼痛、牙齿脱落、听力困难、饮食和睡眠困难、发育不良，以及学习成绩、社会关系和自我表现不佳