Eloranta, A.-M. | bioRxiv Science

bioRxiv2025

A novel Parvimonas OTU is inversely associated with having caries or fillings in children

BackgroundDental caries is the most common chronic oral disease in children, but its etiology is complex and multifactorial. The association of the oral microbiota with caries is underexplored in children. We investigated saliva microbiota in Finnish children and aimed to identify microbial biomarkers associated with the risk of having caries or fillings (CF). MethodsWe examined 400 Finnish children (180 girls, 220 boys) aged 7-9 years who provided stimulated saliva samples and underwent clinical oral examinations at baseline of the Physical Activity and Nutrition in Children study. Of these children, 261 (65%) were with CF and 139 (35%) were without CF. We characterized the saliva microbiota using the 16S rRNA gene sequencing, examined differences in the abundance and composition at the phylum and genus level between these two groups, and studied the associations of selected Operational Taxonomic Units (OTUs) with the risk of having CF in crude and adjusted (OTUs, age, Silness-Loe plaque index) models. ResultsAlpha diversity and richness did not differ between the groups (p>0.1 for Shannon, inverse Simpson, and Chao1 indices) in the total sample nor when analyzed among girls and boys separately. Beta diversity differed between the groups in the total sample, and when girls and boys were analyzed separately (p corrected by false discovery rate method [pcorr] [~] 0.001). In total, 80 OTUs differed between the groups at the genus level (pcorr<0.01). Two OTUs were independently associated with the risk of having CF. A novel Parvimonas OTU was inversely associated with having CF (odds ratio [ORcrude] 0.49, 95% confidence interval [CI] 0.32 to 0.75). In addition, an OTU of probably Streptococcus mutans was positively associated with having CF (ORcrude 6.01, 95% CI 3.49 to 10.36). ConclusionA Parvimonas species represented by a novel OTU is independently and inversely associated with the risk of having CF in children.

microbiology↗

bioRxiv2017

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

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 9 contributing centers. 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 (imputed to Haplotype Reference Consortium or 1000 Genomes phase 1 version 3 panels) accounting for population stratification. Fixed-effects meta-analysis was performed weighted by inverse standard error. Analysis included up to 19,003 individuals (7,530 affected) for primary teeth and 13,353 individuals (5,875 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 to 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.\n\nAuthor summaryDental caries (tooth decay) is a common disease in children. Previous studies suggest genetic factors alter caries risk, but to date there is a gap of knowledge in identifying which specific genetic variants are responsible. We undertook analysis in a consortium including around 19,000 children and investigated whether any of 8 million common genetic variants were associated with risk of caries in primary (milk) or permanent teeth. If identified, these variants are used as tags to highlight genes which may be involved in a disease. We identified variants in two loci associated with caries status; in the primary (rs1594318) and permanent dentition (rs7738851). The former is intronic in ALLC, a gene with poorly understood function. The latter is an intronic variant within NEDD9, a gene which has several known functions including a role in development of craniofacial structures. To gain a more comprehensive understanding of genetic effects which influence caries larger studies and a better understanding of environmental modifiers or interactions with genetic effects are required.

genetics↗