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

ObjectiveA 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. MethodsThe study's community-based sample comprised 212 children (mean age=39months; range=30-52months; 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<5x10(-8) criterion was used for genome-wide significance. SNPs with P<5x10(-5) were followed-up in three independent cohorts of 921 preschool-age children with similar ECC prevalence. ResultsSNPs 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=2.3x10(-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. ConclusionThis study's findings support a heritable component of ECC and demonstrate the feasibility of conducting genomics studies among preschool-age children.