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

龋齿是一种复杂的多因素疾病，其遗传率估计在30%至60%之间。文献表明，许多基因（大多影响较小）可能影响一生中龋齿的患病率和发病率。然而，由于细菌、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，导致龋齿的发生，个体或群体患龋齿的遗传易感性或风险很可能随着时间的推移而受到环境的调节。由于在荟萃分析中汇集了样本量，可以促进个体变异的发现。在本提案中，我们要求基因分型来研究美国不同儿童群体中龋病的发生和进展以及龋病疾病模式的基因，并将研究数据与先前发表的数据结合起来进行荟萃分析。作为家长补助金[5U01DE021412-09（“在初级卫生保健机构中预测从幼儿到学龄儿童的龋齿风险”）]的一部分，正在从目标儿童（1岁至9.5岁）及其主要照顾者那里纵向收集一些人口统计学和非遗传环境和微生物风险因素。父母补助金的目标是开发一种用于初级医疗和牙科保健机构的龋齿风险工具，以确定从幼儿（1-4岁）到学龄（6-9岁）的高龋齿风险儿童；并确定龋齿风险概况和龋齿疾病模式之间的关系。父母资助的主要假设是，除通过风险问卷收集的非临床风险因素外，卫生保健提供者容易识别的临床风险因素（例如，牙间距等），以及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。2019年获得了行政补充（3U01DE021412-09S1），以便进一步收集唾液样本进行基因分型和分析。本CIDR提案的目的是收集全基因组数据，以研究参加父母项目的儿童及其主要照顾者的龋齿经历的遗传学。我们将评估先前确定的与初级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相结合。我们将探讨已确定的遗传关联是否受其他非遗传因素（例如，口腔卫生和饮食风险习惯、氟化物暴露、人口统计学等）的介导。这项研究具有重要意义，因为它有可能加强发现和理解不同人群中负责龋齿发生和进展的遗传变异，以及基因-环境相互作用在龋齿风险中的作用。这一信息可能有助于长期针对龋齿风险增加的人群采取针对性的预防性干预措施。

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.