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.

Public Health Relevance

This project proposes to investigate the genetic underpinning of early childhood caries (ECC), which is the most common chronic childhood disease and an important public health problem. The proposed study will address an important gap in our understanding of ECC's genetic determinants, and for the first time for a genetic study of dental caries, it will include substantial proportions of under-represented minority populations, includin African Americans and Hispanic/Latinos. This study's results have the potential to identify important genes and pathways as candidates for future genetic mechanistic research, and can inform risk stratification and disease prediction for targeting high-risk children with early, intensive caries-preventive protocols.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Wang, Lu
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Dentistry/Oral Hygn
Chapel Hill
United States
Zip Code
Morelli, Thiago; Moss, Kevin L; Preisser, John S et al. (2018) Periodontal profile classes predict periodontal disease progression and tooth loss. J Periodontol 89:148-156
Divaris, Kimon; Joshi, Ashwini (2018) The building blocks of precision oral health in early childhood: the ZOE 2.0 study. J Public Health Dent :
Ballantine, Jami L; Carlson, Jenna C; Ferreira Zandoná, Andrea G et al. (2018) Exploring the genomic basis of early childhood caries: a pilot study. Int J Paediatr Dent 28:217-225
Benecha, Habtamu K; Neelon, Brian; Divaris, Kimon et al. (2017) Marginalized mixture models for count data from multiple source populations. J Stat Distrib Appl 4:3
Pahel, B T; Vann Jr, W F; Divaris, K et al. (2017) A Contemporary Examination of First and Second Permanent Molar Emergence. J Dent Res 96:1115-1121
Divaris, Kimon (2017) Precision Dentistry in Early Childhood: The Central Role of Genomics. Dent Clin North Am 61:619-625
Divaris, Kimon (2017) Fundamentals of Precision Medicine. Compend Contin Educ Dent 38:30-32
Collins, Chimere C; Villa-Torres, Laura; Sams, Lattice D et al. (2016) Framing Young Childrens Oral Health: A Participatory Action Research Project. PLoS One 11:e0161728
Divaris, K (2016) Predicting Dental Caries Outcomes in Children: A ""Risky"" Concept. J Dent Res 95:248-54
Preisser, John S; Das, Kalyan; Long, D Leann et al. (2016) Marginalized zero-inflated negative binomial regression with application to dental caries. Stat Med 35:1722-35