Cohort Profile: ZOE 2.0-A Community-Based Genetic Epidemiologic Study of Early Childhood Oral Health

Abstract

Early childhood caries (ECC) is an aggressive form of dental caries occurring in the first five years of life. Despite its prevalence and consequences, little progress has been made in its prevention and even less is known about individuals' susceptibility or genomic risk factors. The genome-wide association study (GWAS) of ECC ("ZOE 2.0") is a community-based, multi-ethnic, cross-sectional, genetic epidemiologic study seeking to address this knowledge gap. This paper describes the study's design, the cohort's demographic profile, data domains, and key oral health outcomes. Between 2016 and 2019, the study enrolled 8059 3-5-year-old children attending public preschools in North Carolina, United States. Participants resided in 86 of the state's 100 counties and racial/ethnic minorities predominated-for example, 48% (n = 3872) were African American, 22% white, and 20% (n = 1611) were Hispanic/Latino. Seventy-nine percent (n = 6404) of participants underwent clinical dental examinations yielding ECC outcome measures-ECC (defined at the established caries lesion threshold) prevalence was 54% and the mean number of decayed, missing, filled surfaces due to caries was eight. Nearly all (98%) examined children provided sufficient DNA from saliva for genotyping. The cohort's community-based nature and rich data offer excellent opportunities for addressing important clinical, epidemiologic, and biological questions in early childhood.

Keywords: children; community-based studies; early childhood caries; genomics; oral health.

Figure 1

Overview of data domains and measures collected in the ZOE 2.0 study, North Carolina, United States. Adapted with permission from Divaris and Joshi 2020 [20]. To date, supragingival biofilm microbiome analyses have been carried out in a pilot subset of 300 ZOE 2.0 participants (~5% of those with clinical data).

Figure 2

Flowchart of enrollment, clinical examinations, and derivation of the GWAS analytical samples in the ZOE 2.0 study, North Carolina, United States (the 19 participants that are identified with protocol deviations that were withdrawn, or discontinued were initially considered as part of enrollment, but were removed from the study enrollment and do not count towards the reported enrollment figure of 8059).

Figure 3

Monthly and cumulative enrollment during the 30-month enrollment period in the ZOE 2.0 study, North Carolina, United States.

Figure 4

Geographical distribution of participants enrolled in the ZOE 2.0 study across the state of North Carolina, United States.

Figure 5

Monthly and cumulative clinical encounters during the 30-month study period and distribution of time elapsed (months) between enrollment and clinical examination in the ZOE 2.0 study, North Carolina, United States.