GENOTYPING SERVICES USING ILLUMINA GLOBAL DIVERSITY ARRAY (GDA) FOR NIDCR (FONTANA): Genetic markers of caries risk in diverse underserved children

使用 ILLUMINA GLOBAL D多样性阵列 (GDA) 为 NIDCR (FONTANA) 提供基因分型服务：不同服务不足儿童的龋齿风险遗传标记

• 批准号: 10710135
• 负责人: KIM DOHENY
• 金额: $ 13.77万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-25 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10710135
• 关键词: 5 year old; Administrative Supplement; Age; Age-Years; Assessment tool; Behavioral; Caring; Characteristics; Child; Childhood; Chronic Disease; Collection; Complex; Data; Data Analyses; Data Set; Dental; Dental Care; Dental Hygiene; Dental caries; Dentists; Development; Disease; Enrollment; Environment; Environmental Microbiology; Environmental Risk Factor; Fluorides; Genes; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Genotype; Goals; Habits; Health; Health Care Costs; Health Personnel; Heritability; Incidence; Individual; Intervention; Lesion; Life Cycle Stages; Literature; Longevity; Mediating; Medical; Meta-Analysis; Minority Groups; Modeling; Morphology; National Institute of Dental and Craniofacial Research; Odontogenesis; Parents; Pattern; Persons; Policies; Population; Population Group; Population Heterogeneity; Predictive Value; Prevalence; Preventive; Primary Dentition; Primary Health Care; Publishing; Questionnaires; Recording of previous events; Reporting; Request for Proposals; Resources; Risk; Risk Assessment; Risk Factors; Role; Salivary; Sample Size; Sampling; School-Age Population; Services; Therapeutic; Time; Toddler; Tooth structure; Variant; Visit; aged; base; clinical risk; cohort; cost effective; deciduous tooth; demographics; dietary; disparity reduction; ethnic diversity; ethnic minority; experience; gene environment interaction; genetic association; genetic variant; genome-wide; health care delivery; health care settings; innovation; low socioeconomic status; microbial; multidisciplinary; non-genetic; novel; parent grant; parent project; phenotypic data; prevent; preventive intervention; primary caregiver; public health relevance; racial diversity; racial minority; risk prediction; risk variant; saliva sample; sociodemographics; tool

Dental caries is a complex multifactorial disease, with heritability estimated to range from 30% to 60%. The literature suggests that numerous genes, mostly of small effect sizes, are likely to contribute to caries prevalence and incidence over the life span. However, the genetic predisposition or risk for dental caries of an individual or population is very likely modulated over time by the environment, given the complex interplay of bacterial, dietary, salivary, morphological, behavioral, and fluoride exposure-related factors leading to development of dental caries. As sample sizes are pooled in meta-analyses, discoveries of individual variants can be facilitated. In this proposal we request genotyping to investigate genes underlying the development and progression of caries lesions and caries lesion disease patterns in a diverse population of U.S. children, and to combine the study data with previously published data and conduct a meta-analysis. A number of demographic and non-genetic environmental and microbiological risk factors are being collected longitudinally from the targeted children (ages 1 to 9.5), and their primary caregivers, as part of the parent grant [5U01DE021412-09 (“Predicting Caries Risk In Underserved Children, From Toddlers To The School-age Years, In Primary Healthcare Settings”)]. The objective of the parent grant is to develop a caries risk tool for use in primary medical and dental healthcare settings to identify high caries risk children, expanding from the toddler (1-4) to the school-age years (6-9); and to determine the relationships between caries risk profiles and caries disease patterns. The primary hypothesis of the parent grant is that clinical risk factors easily identified by health care providers (e.g., tooth spacing, etc.), in addition to non-clinical risk factors collected through a risk questionnaire, together with information from the life-course trajectory of caries risk, including microbial and other markers, will have strong predictive value for development of caries in children ages 1-9. An administrative supplement (3U01DE021412-09S1) was obtained in 2019 to allow for further collection of salivary samples for genotyping and analysis. The aim of this CIDR proposal is to collect genome-wide data to study the genetics of dental caries experience of children and their primary caregivers enrolled in the parent project. We will assess previously identified genes associated with caries for the primary dentition and combine results of this cohort with external datasets via meta-analysis. We will explore whether identified genetic associations are mediated by other non-genetic factors (e.g., oral hygiene and dietary risk habits, fluoride exposure, demographics, etc.). This study is significant as it has the potential to enhance the discovery and understanding of genetic variants responsible for caries development and progression in diverse population groups, and the role of gene-environment interactions in caries risk. This information may help long-term in targeting preventive interventions to those at increased risk of caries.

龋齿是一种复杂的多因素疾病，遗传率估计为 30% 至 60%。文献表明，许多基因（大部分影响较小）可能会导致整个生命周期的龋齿患病率和发病率。考虑到细菌、饮食、唾液、形态、行为和氟化物暴露相关因素的复杂相互作用，导致龋齿的遗传发育，个人或群体的龋齿倾向或风险很可能随着时间的推移受到环境的调节。由于荟萃分析中汇集了样本量，因此可以促进个体变异的发现，在该提案中，我们要求进行基因分型来研究美国不同人群中龋齿病变和龋齿病变疾病模式的发生和进展的基因。 ，并将研究数据与之前发表的数据相结合，并从目标儿童（1至9.5岁）纵向收集一些人口统计和非遗传环境和微生物风险因素，及其主要照顾者，作为家长补助金的一部分 [5U01DE021412-09（“在初级医疗机构中预测服务不足的儿童，从幼儿到学龄期的龋齿风险”）]。用于初级医疗和牙科保健机构的龋齿风险工具，用于识别高龋齿风险儿童，范围从幼儿（1-4）到学龄期（6-9）；并确定其关系；龋齿风险概况和龋齿疾病模式之间的关系 家长补助金的主要假设是，除了通过风险调查问卷收集的非临床风险因素外，医疗保健提供者还可以轻松识别临床风险因素（例如牙齿间距等）。连同来自龋齿风险生命历程轨迹的信息，包括微生物和其他标记物，将对 1-9 岁儿童的龋齿发展具有很强的预测价值。 (3U01DE021412-09S1) 于 2019 年获得，以便进一步收集唾液样本进行基因分型和分析。该 CIDR 提案的目的是收集全基因组数据，以研究登记的儿童及其主要照顾者的龋齿经历的遗传学。在父项目中，我们将评估先前确定的与乳牙列龋齿相关的基因，并通过荟萃分析将该队列的结果与外部数据集结合起来，探讨是否已确定的遗传关联。是由其他非遗传因素（例如口腔卫生和饮食风险习惯、氟化物暴露、人口统计等）介导的。这项研究具有重要意义，因为它有可能增强对导致龋齿发生和发展的遗传变异的发现和理解。以及基因与环境相互作用在龋齿风险中的作用，这些信息可能有助于长期针对龋齿风险较高的人群采取预防干预措施。