Exploring the genomic basis of early childhood caries: a pilot study

Objective: A genetic component in early childhood caries (ECC) is theorized, but no genome-wide investigations of ECC have been conducted. This pilot study is part of a long-term research program aimed to: (1) determine the proportion of ECC variance attributable to the human genome and (2) identify ECC-associated genetic loci. Methods: The study's community-based sample comprised 212 children (mean age=39 months; range = 30–52 months; males = 55%; Hispanic/Latino = 35%, African-American = 32%; American Academy of Pediatric Dentistry definition of ECC prevalence = 38%). Approximately 2.4 million single nucleotide polymorphisms (SNPs) were genotyped using DNA purified from saliva. A P < 5 × 10−8 criterion was used for genome-wide significance. SNPs with P < 5 × 10−5 were followed-up in three independent cohorts of 921 preschool-age children with similar ECC prevalence. Results: SNPs with minor allele frequency ≥5% explained 52% (standard error = 54%) of ECC variance (one-sided P = 0.03). Unsurprisingly, given the pilot's small sample size, no genome-wide significant associations were found. An intergenic locus on 4q32 (rs4690994) displayed the strongest association with ECC [P = 2.3 × 10−6; odds ratio (OR) = 3.5; 95% confidence interval (CI) = 2.1–5.9]. Thirteen loci with suggestive associations were followed-up – none showed evidence of association in the replication samples. Conclusion: This study's findings support a heritable component of ECC and demonstrate the feasibility of conducting genomics studies among preschool-age children

Genes and Their Effects on Dental Caries May Differ between Primary and Permanent Dentitions

The importance of genetic factors in the genesis of dental caries of both primary and permanent dentitions is well established; however, the degree to which genes contribute to the development of dental caries, and whether these genes differ between primary and permanent dentitions, is largely unknown. Using family-based likelihood methods, we assessed the heritability of caries-related phenotypes for both children and adults in 2,600 participants from 740 families. We found that caries phenotypes in the primary dentition were highly heritable, with genes accounting for 54–70% of variation in caries scores. The heritability of caries scores in the permanent dentition was also substantial (35–55%, all p < 0.01), although this was lower than analogous phenotypes in the primary dentition. Assessment of the genetic correlation between primary and permanent caries scores indicated that 18% of the covariation in these traits was due to common genetic factors (p < 0.01). Therefore, dental caries in primary and permanent teeth may be partly attributable to different suites of genes or genes with differential effects. Sex and age explained much of the phenotypic variation in permanent, but not primary, dentition. Further, including pre-cavitated white-spot lesions in the phenotype definition substantially increased the heritability estimates for dental caries. In conclusion, our results show that dental caries are heritable, and suggest that genes affecting susceptibility to caries in the primary dentition may differ from those in permanent teeth. Moreover, metrics for quantifying caries that incorporate white-spot lesions may serve as better phenotypes in genetic studies of the causes of tooth decay