Genome-Wide Association Study of Early Childhood Caries

儿童早期龋齿的全基因组关联研究

基本信息

批准号：
8985395
负责人：
Kimon Divaris
金额：
$ 115.13万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-10 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8985395
关键词：
12 year old 4 year old Address Adult Affect African African American Age American Area Behavior Behavioral Caring Characteristics Child Childhood Chronic Chronic Disease Clinical Clinical Data Collaborations Communities Community Health Systems Complex Coronary heart disease DNA Data Dental Dental Care Dental Enamel Hypoplasia Dental Plaque Dental caries Detection Diagnosis Diagnostic Disease Economically Deprived Population Economics Enrollment Epidemiologic Studies Epidemiology Ethnic group Etiology European Family Funding Future General Anesthesia Genes Genetic Genetic Determinism Genetic Structures Genetic study Genome Genomics Genotype Head Start Program Health Healthcare Heritability Hispanics Human International Investigation Knowledge Latino Lesion Life Cycle Stages Low Income Population Measures Meta-Analysis Morbidity - disease rate Non-Insulin-Dependent Diabetes Mellitus North Carolina Nursery Schools Parents Pathway interactions Pattern Personal Satisfaction Phenotype Population Preschool Child Prevalence Preventive Primary Dentition Procedures Protocols documentation Public Health Regulatory Element Reporting Research Research Infrastructure Risk Risk Factors Saliva Sample Size Sampling Sedation procedure Severities Social Impacts Stratification Surveys System Techniques Testing Time Tooth Diseases Tooth structure Underrepresented Minority Visual system structure Vulnerable Populations age group aged base burden of illness cohort deciduous tooth density early childhood early onset economic cost economic impact experience falls follow-up genetic information genetic variant genome wide association study high risk improved insight knowledge base microbiome novel permanent tooth population based prevent public health relevance racial and ethnic racial disparity response restorative treatment risk variant sample collection secondary outcome social tooth surface trait

项目摘要

DESCRIPTION (provided by applicant): Early childhood caries (ECC) is the most common chronic disease of childhood, and one that is characterized by marked social, economic, and racial disparities. The prevalence of ECC in the US increased by 15% during the last 2 decades, and according to the most recent national data 28% of children ages 2-5 are affected. Importantly, management of ECC among young children often requires complex and costly restorative procedures with the use of advanced behavior management techniques including sedation and general anesthesia. ECC can have severe sequelae for children's general health and well-being, and confers important social and economic impacts on their families, communities, and the health system. Caries is a multifactorial disease with a substantial genetic component, which is estimated between 40-60%, but little is known regarding specific contributing genetic factors. A large-scale genome-wide association study (GWAS) involving a multi-cohort meta-analysis recently nominated 29 loci as associated with dental caries among adult, predominantly European-American (EA), populations. So far, the only GWAS examining caries in the primary dentition employed a sample of 1,300 3-12 year-old EA children and nominated 7 genes, 2 of which showed additional evidence of association in follow-up studies among children and adults. Here, we propose to conduct a large-scale GWAS of ECC involving a multi-ethnic community-based sample of 6,000 children ages 3 and 4. For Aim 1, we will undertake a comprehensive clinical dental characterization of a state-representative sample of approximately 6,000 children enrolled in Early Head Start and Head Start programs in North Carolina. We will use a tested clinical examination protocol including saliva sample collection for DNA extraction, and will use the latest International Caries Diagnosis System (ICDAS) visual diagnostic criteria to determine disease prevalence and severity. We will collect and store dental plaque samples for future microbiome analyses that will be funded separately. To identify genetic variants that are associated with ECC, in Aim 2, we will conduct a trans-ethnic GWAS of ECC and related traits, utilizing high-density genotyping, imputation to 1000 Genomes Project reference panels and advanced statistical approaches to leverage differences in genetic structure between racial/ethnic groups. In Aim 3, we will utilize publicly available GWAS data of early childhood and adult caries, to determine the racial/ethnic and age-group generalization/transferability of loci, genes, and gene sets/pathways identified in our study. Our group's experience in conducting dental epidemiologic studies among young children including an ongoing collaboration with EHS/HS and expertise in large-scale, multi-ethnic GWAS, create a unique opportunity to carry out this important investigation and advance the knowledge base of genomics of dental caries. The study will improve our understanding of ECC's epidemiology and genomic etiology, key knowledge to reduce the burden of disease in populations of young children, including those underrepresented in research.

描述（由适用提供）：幼儿汽车（ECC）是最常见的童年慢性疾病，其特征是社会，经济和种族分布明显。在过去的20年中，美国ECC的患病率增加了15％，根据最新数据，2-5岁儿童的28％受到影响。重要的是，幼儿对ECC的管理通常需要使用先进的行为管理技术（包括镇静和全身麻醉），需要复杂而昂贵的修复程序。 ECC可以为儿童的一般健康和福祉而患有严重的后遗症，并赋予对家庭，社区和卫生系统的重要社会和经济影响。龋齿是一种多因素疾病，具有实质性的遗传成分，估计在40-60％之间，但在特定的促进遗传因素方面鲜为人知。一项大规模基因组关联研究（GWAS），涉及一项多多局部荟萃分析，最近提名了29个位置，与成年人（主要是欧洲裔美国人（EA），人口）中的牙科车相关。到目前为止，在初级牙列中检查汽车的唯一GWA进行了1,300个3-12岁的EA儿童和提名的7个基因样本，其中2个在儿童和成人的后续研究中显示了其他相关性证据。在这里，我们建议进行大规模的ECC大规模GWA，涉及6,000名3岁和4岁儿童的多种族基于社区的样本。对于AIM 1，我们将对北卡罗来纳州的大约6,000名在早期启动和头启动计划中招募的大约6,000名儿童进行全面的临床牙齿表征。我们将使用经过测试的临床检查方案，包括 DNA提取，并将使用最新的国际龋齿诊断系统（ICDAS）视觉诊断标准来确定疾病的患病率和严重程度。我们将收集和存储牙菌斑样品，以进行未来的微生物组分析，这些分析将分别资助。为了鉴定与EAM 2相关的遗传变异，我们将使用高密度基因分型，对1000个基因组项目参考面板进行估算，并进行高级统计方法，以利用种族/each族之间的遗传结构差异。在AIM 3中，我们将利用幼儿和成人汽车的公开可用的GWAS数据，以确定我们研究中确定的局部，基因和基因/途径的种族/族裔和年龄群概括/转移性。我们小组在幼儿进行牙科流行病学研究方面的经验，包括与EHS/HS进行的持续合作以及在大规模多种族GWAS方面的专业知识，创造了一个独特的机会来进行这项重要的投资并推进牙科携带基因组学知识基础。这项研究将提高我们对ECC流行病学和基因组病因学的理解，这是减少幼儿人群中疾病伯宁（包括研究不足的人群）的关键知识。