Dataset Information

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

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.

SUBMITTER: Ballantine JL

PROVIDER: S-EPMC5811369 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Ballantine Jami L JL Carlson Jenna C JC Ferreira Zandoná Andrea G AG Agler Cary C Zeldin Leslie P LP Rozier Richard Gary RG Roberts Michael W MW Basta Patricia V PV Luo Jason J Antonio-Obese Mikafui E ME McNeil Daniel W DW Weyant Robert J RJ Crout Richard J RJ Slayton Rebecca L RL Levy Steven M SM Shaffer John R JR Marazita Mary L ML North Kari E KE Divaris Kimon K

International journal of paediatric dentistry 20171023 2

<h4>Objective</h4>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.<h4>Methods</h4>The study's community-based sample comprised 212 children (mean age=39 months; range = 30-52 months; males = 55%; Hispanic/Latino = 35%, African-Ame ...[more]

PMID: 29057527

Similar Datasets

Project description:BackgroundOral diseases, such as early childhood caries (ECC), have a complex etiology with common, behaviour-related risk factors. Appropriately targeted behavioural intervention using effective tools can help to eliminate risk behaviour leading to ECC. The aim of this study was to ascertain which visual stimuli with a supporting text evoke the strongest emotional response in infants' mothers and, therefore, are suitable candidates for inclusion in behavioural interventions within the prevention of ECC.MethodsThirty-nine mothers of one-year-old children who filled out an originally designed electronic questionnaire, containing 20 visual stimuli with accompanying texts related to dental caries (10/10 with positive/negative intended emotional response), were included in this cross-sectional study. The emotional impact of each stimulus in the mothers was evaluated using the Self-Assessment Manikin (SAM) technique, which represents three emotional dimensions: valence, arousal, and dominance.ResultsEach of the stimuli was assessed by the mothers of infants based on its emotional impact. The real emotional response (evaluated according to the median of valence) was in line with the primarily intended response in 90% of cases (p < 0.05). The text with a warning evoked a greater emotional response (evaluated according to the median of arousal) in mothers than only the informative instruction (p < 0.05). The relationship between arousal and valence (r = - 0.99; p < 0.05) indicates that the more aversive stimuli raise higher arousal. The significant correlation between valence and dominance shows that the more positive the stimuli, the higher feeling of control over the evoked emotion the mothers have (r = 0.83; p < 0.05), and, on the contrary, the lowest control over emotion is correlated with higher arousal (r = - 0.85; p < 0.05). Generally, mothers rated themselves as in high control of their emotions over the individual stimuli.ConclusionsThis pilot study proved that negative pictorial and text warnings about the risks of developing caries had the potential to evoke strong emotional responses in the mothers of infants. We identified three visual stimuli that could be included in future extensive motivation material in an attempt to affect the preventive behaviour of mothers, and thus the oral health of their infants.

Project description:Early childhood caries (ECC) is the most common noncommunicable childhood disease-an important health problem with known environmental and social/behavioral influences lacking consensus genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multiancestry population of U.S. preschool-age children (N = 6,103) ages 3 to 5 y participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used International Caries Detection and Assessment System criteria to measure ECC; the primary trait was the number of primary tooth surfaces with caries experience (i.e., dmfs index). We estimated heritability and concordance rates and conducted genome-wide association analyses to estimate overall genetic effects as well as stratified by sex, household water fluoride, and dietary sugar and leveraged combined gene/gene-environment effects using 2-degree-of-freedom joint tests. Common genetic variants explained 24% of ECC phenotypic variance among unrelated individuals, while concordance rates were 0.64 (95% confidence interval [CI] = 0.42-0.79) among monozygotic twins and 0.44 (95% CI = 0.34-0.53) among first-degree relatives. Across all analyses, we identified 21 novel nonoverlapping genome-wide significant loci (P < 5 × 10-8) and 1 genome-wide significant gene (TAAR6) associated with ECC. The taste receptor activity gene set, with known roles in chemosensing, bacterial recognition, and innate immunity in the oral cavity, was strongly associated with ECC. While no locus remained significant after studywise multiple-testing correction, 3 loci were nominally significant (P < 0.05) and directionally consistent in external cohorts of 285,248 adults (rs1442369, DLGAP1 and rs74606067, RP11-856F16.2) and 18,994 children (rs71327750, SLC41A3). Meanwhile, the strongest marker known to be associated with adult caries (rs1122171, tagging the long noncoding RNA PITX1-AS1) was nominally significant (P = 0.01) and directionally consistent with ECC in our study. Taken together, the results of this study add to the genomics knowledge base for early childhood caries, offer several plausible candidates for future mechanistic studies, and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations.

Project description:BackgroundEarly childhood caries (ECC) is a rapidly progressing form of dental infection and a significant public health problem, especially among socially and economically disadvantaged populations. This study aimed to assess the risk factors for ECC among a cohort of Sub-Saharan African children and to determine the role of genetics in the etiology of ECC.MethodsA sample of 691 children (338 with ECC, 353 without ECC, age < 6 years) was recruited from schools in Lagos, Nigeria. Socio-demographic, dental services utilization and infant dietary data were obtained with interviewer-administered questionnaire. Oral examination was conducted using the WHO oral health diagnostic criteria. Saliva samples were collected from the children for genetic analysis. Single nucleotide polymorphisms were selected from previous study for genotyping. Genetic association analyses to investigate the role of genetics in the etiology of ECC was done. Bivariate comparisons and Multivariate logistic regression analyses were conducted to assess associations between ECC and predictor variables, p < 0.05.ResultsOf the 338 children with ECC, 64 (18.9%) had Severe-Early Childhood Caries (S-ECC). Children aged 48-59 months comprised the highest proportion of subjects with ECC (165; 48.8%) and S-ECC (24; 37.5%) while female subjects had higher dt (3.13 ± 2.56) and dmft values 3.27 ± 2.64. ECC was significantly more prevalent among children who were breastfed at night ≥ 12 months (OR 3.30; CI 0.39, 4.75), those with no previous dental visit (OR 1.71; CI 0.24, 2.77), those who used sweetened pacifiers (OR 1.85; CI 0.91, 3.79) and those who daily consumed sugar-sweetened drinks/snacks (OR 1.35; CI 0.09, 18.51). A suggestive increased risk for ECC (OR 1.26, p = 0. 0.0397) was observed for the genetic variant rs11239282 on chromosome 10. We also observed a suggestive reduced risk for ECC (OR 0.80, p = 0.03) for the rs131777 on chromosome 22. None of the genetic variants were significant after correction for multiple testing (Bonferroni p value p = 0.004).ConclusionsProlonged night-time breastfeeding, poor utilization of dental services and daily consumption of sugar were risk factors for ECC. Larger sample size is needed to confirm the results of the genetic analysis and to conduct genome wide studies in order to discover new risk loci for ECC.

Project description:Dental caries is characterized by a dysbiotic shift at the biofilm-tooth surface interface, yet comprehensive biochemical characterizations of the biofilm are scant. We used metabolomics to identify biochemical features of the supragingival biofilm associated with early childhood caries (ECC) prevalence and severity. The study's analytical sample comprised 289 children ages 3 to 5 (51% with ECC) who attended public preschools in North Carolina and were enrolled in a community-based cross-sectional study of early childhood oral health. Clinical examinations were conducted by calibrated examiners in community locations using International Caries Detection and Classification System (ICDAS) criteria. Supragingival plaque collected from the facial/buccal surfaces of all primary teeth in the upper-left quadrant was analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. Associations between individual metabolites and 18 clinical traits (based on different ECC definitions and sets of tooth surfaces) were quantified using Brownian distance correlations (dCor) and linear regression modeling of log2-transformed values, applying a false discovery rate multiple testing correction. A tree-based pipeline optimization tool (TPOT)-machine learning process was used to identify the best-fitting ECC classification metabolite model. There were 503 named metabolites identified, including microbial, host, and exogenous biochemicals. Most significant ECC-metabolite associations were positive (i.e., upregulations/enrichments). The localized ECC case definition (ICDAS ≥1 caries experience within the surfaces from which plaque was collected) had the strongest correlation with the metabolome (dCor P = 8 × 10-3). Sixteen metabolites were significantly associated with ECC after multiple testing correction, including fucose (P = 3.0 × 10-6) and N-acetylneuraminate (p = 6.8 × 10-6) with higher ECC prevalence, as well as catechin (P = 4.7 × 10-6) and epicatechin (P = 2.9 × 10-6) with lower. Catechin, epicatechin, imidazole propionate, fucose, 9,10-DiHOME, and N-acetylneuraminate were among the top 15 metabolites in terms of ECC classification importance in the automated TPOT model. These supragingival biofilm metabolite findings provide novel insights in ECC biology and can serve as the basis for the development of measures of disease activity or risk assessment.

Dataset Information

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

Objective

Methods

Results

Conclusion

Publications

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

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