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

Authors: Ballantine, Jami L; Carlson, Jenna C; Ferreira Zandoná, Andrea G; Agler, Cary; Zeldin, Leslie P; Rozier, Richard Gary; Roberts, Michael W; Basta, Patricia V; Luo, Jason; Antonio-Obese, Mikafui E; McNeil, Daniel W; Weyant, Robert J; Crout, Richard J; Slayton, Rebecca L; Levy, Steven M; Shaffer, John R; Marazita, Mary L; North, Kari E; Divaris, Kimon

Published In Int J Paediatr Dent, (2018 Mar)

Abstract: 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.

PubMed ID: 29057527

MeSH Terms: Child, Preschool; Dental Caries/epidemiology; Dental Caries/genetics*; Female; Gene Frequency/genetics; Genetic Association Studies; Genetic Predisposition to Disease/genetics; Humans; Male; North Carolina/epidemiology; Pilot Projects; Polymorphism, Single Nucleotide/genetics; Prevalence