Project Abstract Caries that occur in the primary dentition of children aged under 6 years, or early childhood caries (ECC), affect more than one-fifth of US children aged 2-5. ECC is a multifactorial disease: the oral microbiome, host behaviors and genetic factors influence caries risk. Preventing ECC can improve oral and systemic health and reduce healthcare burden across the life course. By better understanding the causal mechanisms of ECC we may be able to improve upon prevention and intervention efforts. We will use already collected human genotypes, salivary and dental plaque microbiome, and sociodemographic and behavioral data from children participating in the Center for Oral Health Research in Appalachia cohort 2 to: 1) compare data reduction methods for characterizing the developing salivary microbiome, 2) assess the relationships between early-life exposures, the early-life oral microbiome and ECC, and 3) test for effect modification of the oral microbiomes’ relationship with ECC by host genetic caries risk. The proposed study has the potential to identify environmental and microbial factors which encourage or discourage the development of a cariogenic oral microbiome and to identify human genetic subpopulations for whom interventions on the oral microbiome may be especially effective. With this research proposal and training plan the applicant will gain skills in longitudinal analysis of high-dimensional data, processing of microbial and human genetic data and gain expertise in the multifactorial etiology of dental caries. The proposed training will support the applicant’s long-term goal of becoming an independent researcher focusing on the interplay between microbial, behavioral and human genetic factors in the development of oral disease. This project is consistent with NIDCR 2030 goals of Precision Health, Autotherapies and Oral Health + Overall Health.