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