Candidate genes and replication studies of dental caries

Motivation: Dental caries (cavities) constitutes as a significant public health problem that begins in early childhood and that is steadily increasing in the US. It remains the most common chronic childhood disease, five times more common than asthma and four times more common than childhood obesity. Untreated caries disproportionately affects low socioeconomic populations and some racial/ethnic minority groups. Furthermore, dental caries is a multifactorial disease that involves many interacting variables to promote its development. Unlike other diseases, dental caries is highly preventable. However, there are still some individuals who seem to be more susceptible to caries, and those who appear to be extremely resistant, thus implying a genetic component. Therefore, we investigated a subset of genes that have some biologically plausible role in oral health for evidence of association with dental caries experience in 13 race- and age-stratified samples from six independent studies (n =3600).\ud Methods: Participants were genotyped for a custom panel of single nucleotide polymorphisms (SNPs) using the Illumina Golden Gate platform by the Center for Inherited Disease Research (CIDR). We tested association of these genes with dental caries in 13 race- and age-stratified samples from six independent studies of whites and blacks adults and children. We performed analyses independently for each cohort and synthesized results by meta-analysis across five childhood cohorts and across eight adult cohorts. \ud Results: Linear regression used to detect genetic association for a selection of candidate ion channel genes revealed two SNPs in CACNA2D1 were significantly associated with dental caries via meta-analysis across the five childhood cohorts, and in one individual childhood cohort (p < 7.1 x 10-4). In adults, genetic association was observed in three individual cohorts for potassium channel genes KCNH1 and KCNK5 (p-values