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

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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.