Exome-wide Rare Variant Analysis of Early Childhood Caries

Objectives: Early childhood caries is a complex disease with multiple environmental and genetic components. The aim of this study was to investigate whether rare coding variants associate with early childhood caries.
Methods: We performed a rare variant analysis of the binary early childhood caries phenotype in 814 unrelated Caucasian children, age 0-6, who were drawn from the Center for Oral Health Research in Appalachia (COHRA2). Approximately 240,000 coding variants were genotyped on the Illumina Infinium Exome-24v1-0 BeadChip. Exome-wide variants with frequencies <1% were analyzed through gene-based tests, SKAT and CMC. Analyses were adjusted for age, sex, and study site.
Results: 100 cases and 714 controls were included. Upon multiple testing correction, two genes showed evidence of association via the CMC test: the genes BLNK (p=2.67E-07) and F3 (p=9.36E-07). Neither of these genes appear to have plausible connections to dental caries. Several additional genese were nominally significant.
Conclusions: These results suggest that rare variants in BLNK and F3 may play a role in early childhood caries. These results should be replicated in additional studies.