Investigating the genetics of dental caries incidence, development over time, and variability

Dental caries is the most common chronic disease of childhood, worldwide. A better understanding of the etiology of dental caries is needed to improve caries prevention and oral health at both individual and population levels. This study performed GWASs using phenotypes including time-to-first caries incidence and repeated caries measurements at multiple time points, and conducted genome-wide scans of heteroscedasticity in dental caries experience followed by targeted gene-by-environment interaction (GEI) modeling. Genome-wide survival analysis in Aim 1 showed the genetic underpinnings of caries incidence, with heritability (i.e., the proportion of variance explained by genetics) of time-to-first caries estimated to be 54.4% and 14 association signals identified at the suggestive level (P<1E-5), some of which were located near genes with potential roles in dental caries, including COL5A1, ASIC2, and ESR1. GWAS of repeated dental caries measurements in Aim 2 was the first longitudinal GWAS of caries that demonstrated the genetic influence on caries development over time. The heritability estimate of longitudinal caries trajectories was 54.7%, and there were 1 genome-wide (P<5E-8) and 12 suggestive (P