Consortium-based genome-wide meta-analysis for childhood dental caries traits

Abstract

Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5–18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

Measuring the Microscopic Structures of Human Dental Enamel Can Predict Caries Experience

“…The most recent example is a meta-analysis of studies that include dental caries assessments ranging from self-reported questionnaire to standard clinical examinations for more than 13,000 children 2 to 18 years of age. The reduction of the phenotype to having at least one lesion versus having no lesions from scores obtained in primary and permanent dentitions led, not surprisingly, to meaningless results [19]. Here, we are reporting how differences observed in the enamel surface measured through scanning electron microscopy without any known bias on how these measurements were generated associate with genetic variants in genes previously associated with dental caries from hypothesis driven work.…”

Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

“…Genome-wide association studies (GWAS) for dental caries have investigated measures, including overall caries experience 6,7 , specific presentations of disease and the presence or absence of disease in paediatric populations 8,9 . To date, few reliable genetic-association signals have been found, and this is likely to reflect different measurement approaches used, complex genetic architecture 10 of dental caries or limited statistical power to detect associations.…”

Using big data to promote precision oral health in the context of a learning healthcare system

“…Repositories such as the Human Oral Microbiome database and the Human Microbiome Consortium have emerged as data aggregate to provide standardized and easily accessible sources of oral microbiome genomic and taxonomic data to researchers and clinicians alike . Genome‐wide association studies have also been performed on traditionally at‐risk populations such as US Hispanics and children to further identify characteristics that can be used to stratify these patients . However, the relationship between genetics and caries risk is still unclear.…”

“…63,64 Genome-wide association studies have also been performed on traditionally at-risk populations such as US Hispanics and children to further identify characteristics that can be used to stratify these patients. 65,66 However, the relationship between genetics and caries risk is still unclear. Currently, these studies have only found modest associations between gene variants and caries risk.…”