Pilot GWAS of caries in African-Americans shows genetic heterogeneity.

BACKGROUND: Dental caries is the most common chronic disease in the US and disproportionately affects racial/ethnic minorities. Caries is heritable, and though genetic heterogeneity exists between ancestries for a substantial portion of loci associated with complex disease, a genome-wide association study (GWAS) of caries specifically in African Americans has not been performed previously. METHODS: We performed exploratory GWAS of dental caries in 109 African American adults (age > 18) and 96 children (age 3-12) from the Center for Oral Health Research in Appalachia (COHRA1 cohort). Caries phenotypes (DMFS, DMFT, dft, and dfs indices) assessed by dental exams were tested for association with 5 million genotyped or imputed single nucleotide polymorphisms (SNPs), separately in the two age groups. The GWAS was performed using linear regression with adjustment for age, sex, and two principal components of ancestry. A maximum of 1 million adaptive permutations were run to determine empirical significance. RESULTS: No loci met the threshold for genome-wide significance, though some of the strongest signals were near genes previously implicated in caries such as antimicrobial peptide DEFB1 (rs2515501; p = 4.54 × 10- 6) and TUFT1 (rs11805632; p = 5.15 × 10- 6). Effect estimates of lead SNPs at suggestive loci were compared between African Americans and Caucasians (adults N = 918; children N = 983). Significant (p < 5 × 10- 8) genetic heterogeneity for caries risk was found between racial groups for 50% of the suggestive loci in children, and 12-18% of the suggestive loci in adults. CONCLUSIONS: The genetic heterogeneity results suggest that there may be differences in the contributions of genetic variants to caries across racial groups, and highlight the critical need for the inclusion of minorities in subsequent and larger genetic studies of caries in order to meet the goals of precision medicine and to reduce oral health disparities.

Prenatal sex hormones, digit ratio, and face shape in adult males.

OBJECTIVES: Several reports have demonstrated a relationship between second to fourth digit ratio (2D:4D) and facial shape, suggesting that prenatal sex hormones play a role in the development of the craniofacial complex. Using 3D surface imaging and geometric morphometrics, we test the hypothesis that decreased digit ratio (indicative of increased prenatal androgen exposure) is associated with a more masculine facial phenotype. METHODS: 3D facial surface images and digit measures were collected on a sample of 151 adult males. Facial landmarks collected from the images were aligned by Procrustes superimposition and the resulting shape coordinates regressed on 2D:4D. Variations in facial shape related to 2D:4D were visualized with deformable surface warps. RESULTS: A significant statistical relationship was observed between facial shape variation and 2D:4D (p = 0.0084). Lower 2D:4D ratio in adult males was associated with increased facial width relative to height, increased mandibular prognathism, greater nasal projection, and increased upper and lower lip projection. CONCLUSIONS: A statistical relationship between 2D:4D and facial shape in adult males was observed. Faces tended to look more masculine as 2D:4D decreased, suggesting a biologically plausible link between prenatal androgen exposure and the development of male facial characteristics.

Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.

Dental caries continues to be the most common chronic disease in children today. Despite the substantial involvement of genetics in the process of caries development, the specific genes contributing to dental caries remain largely unknown. We performed separate genome-wide association studies of smooth and pit-and-fissure tooth surface caries experience in the primary dentitions of self-reported white children in two samples from Iowa and rural Appalachia. In total, 1,006 children (ages 3-12 years) were included for smooth surface analysis, and 979 children (ages 4-14 years) for pit-and-fissure surface analysis. Associations were tested for more than 1.2 million single nucleotide polymorphisms, either genotyped or imputed. We detected genome-wide significant signals in KPNA4 (p value = 2.0E-9), and suggestive signals in ITGAL (p value = 2.1E-7) and PLUNC family genes (p value = 2.0E-6), thus nominating these novel loci as putative caries susceptibility genes. We also replicated associations observed in previous studies for MPPED2 (p value = 6.9E-6), AJAP1 (p value = 1.6E-6) and RPS6KA2 (p value = 7.3E-6). Replication of these associations in additional samples, as well as experimental studies to determine the biological functions of associated genetic variants, are warranted. Ultimately, efforts such as this may lead to a better understanding of caries etiology, and could eventually facilitate the development of new interventions and preventive measures.

A Polygenic Score Predicts Caries Experience in Elderly Swedish Adults.

Caries is a partially heritable disease, raising the possibility that a polygenic score (PS, a summary of an individual's genetic propensity for disease) might be a useful tool for risk assessment. To date, PS for some diseases have shown clinical utility, although no PS for caries has been evaluated. The objective of the study was to test whether a PS for caries is associated with disease experience or increment in a cohort of Swedish adults. A genome-wide PS for caries was trained using the results of a published genome-wide association meta-analysis and constructed in an independent cohort of 15,460 Swedish adults. Electronic dental records from the Swedish Quality Registry for Caries and Periodontitis (SKaPa) were used to compute the decayed, missing, and filled tooth surfaces (DMFS) index and the number of remaining teeth. The performance of the PS was evaluated by testing the association between the PS and DMFS at a single dental examination, as well as between the PS and the rate of change in DMFS. Participants in the highest and lowest deciles of PS had a mean DMFS of 63.5 and 46.3, respectively. A regression analysis confirmed this association where a 1 standard deviation increase in PS was associated with approximately 4-unit higher DMFS (P < 2 × 10-16). Participants with the highest decile of PS also had greater change in DMFS during follow-up. Results were robust to sensitivity analysis, which adjusted for age, age squared, sex, and the first 20 genetic principal components. Mediation analysis suggested that tooth loss was a strong mediating factor in the association between PS and DMFS but also supported a direct genetic effect on caries. In this cohort, there are clinically meaningful differences in DMFS between participants with high and low PS for caries. The results highlight the potential role of genomic data in improving caries risk assessment.

Multi-ancestry Genome-Wide Association Study of Early Childhood Caries.

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namely RP11-856F16 . 2 (rs74606067) and SLC41A3 (rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identified TAAR6 as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.

Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries.

Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1-5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.

Bacterial Community Modifies Host Genetics Effect on Early Childhood Caries.

By age 5, approximately one-fifth of children have early childhood caries (ECC). Both the oral microbiome and host genetics are thought to influence susceptibility. Whether the oral microbiome modifies genetic susceptibility to ECC has not been tested. We test whether the salivary bacteriome modifies the association of a polygenic score (PGS, a score derived from genomic data that summarizes genetic susceptibility to disease) for primary tooth decay on ECC in the Center for Oral Health Research in Appalachia 2 longitudinal birth cohort. Children were genotyped using the Illumina Multi-Ethnic Genotyping Array and underwent annual dental examinations. We constructed a PGS for primary tooth decay using weights from an independent, genome-wide association meta-analysis. Using Poisson regression, we tested for associations between the PGS (high versus low) and ECC incidence, adjusting for demographic characteristics (n = 783). An incidence-density sampled subset of the cohort (n = 138) had salivary bacteriome data at 24 mo of age. We tested for effect modification of the PGS on ECC case status by salivary bacterial community state type (CST). By 60 mo, 20.69% of children had ECC. High PGS was not associated with an increased rate of ECC (incidence rate ratio, 1.09; 95% confidence interval [CI], 0.83-1.42). However, having a cariogenic salivary bacterial CST at 24 mo was associated with ECC (odds ratio [OR], 7.48; 95% CI, 3.06-18.26), which was robust to PGS adjustment. An interaction existed between the salivary bacterial CST and the PGS on the multiplicative scale (P = 0.04). The PGS was associated with ECC (OR, 4.83; 95% CI, 1.29-18.17) only among individuals with a noncariogenic salivary bacterial CST (n = 70). Genetic causes of caries may be harder to detect when not accounting for cariogenic oral microbiomes. As certain salivary bacterial CSTs increased ECC risk across genetic risk strata, preventing colonization of cariogenic microbiomes would be universally beneficial.

Genetic susceptibility to dental caries on pit and fissure and smooth surfaces.

Carious lesions are distributed nonuniformly across tooth surfaces of the complete dentition, suggesting that the effects of risk factors may be surface-specific. Whether genes differentially affect caries risk across tooth surfaces is unknown. We investigated the role of genetics on two classes of tooth surfaces, pit and fissure surfaces (PFS) and smooth surfaces (SMS), in more than 2,600 subjects from 740 families. Participants were examined for surface-level evidence of dental caries, and caries scores for permanent and/or primary teeth were generated separately for PFS and SMS. Heritability estimates (h(2), i.e. the proportion of trait variation due to genes) of PFS and SMS caries scores were obtained using likelihood methods. The genetic correlations between PFS and SMS caries scores were calculated to assess the degree to which traits covary due to common genetic effects. Overall, the heritability of caries scores was similar for PFS (h(2) = 19-53%; p < 0.001) and SMS (h(2) = 17-42%; p < 0.001). Heritability of caries scores for both PFS and SMS in the primary dentition was greater than in the permanent dentition and total dentition. With one exception, the genetic correlation between PFS and SMS caries scores was not significantly different from 100%, indicating that (mostly) common genes are involved in the risk of caries for both surface types. Genetic correlation for the primary dentition dfs (decay + filled surfaces) was significantly less than 100% (p < 0.001), indicating that genetic factors may exert differential effects on caries risk in PFS versus SMS in the primary dentition.

Genetic and environmental factors associated with dental caries in children: the Iowa Fluoride Study.

Dental caries remains the most common chronic childhood disease. Despite strong evidence of genetic components, there have been few studies of candidate genes and caries. In this analysis we tried to assess genetic and environmental factors contributing to childhood caries in the Iowa Fluoride Study. Environmental factors (age, sex, race, tooth-brushing frequencies and water fluoride level) and three dental caries scores (d(2)fs-total, d(2)fs-pit/fissure, and d(2)fs-smooth surface) were assessed in 575 unrelated children (mean age 5.2 years). Regression analyses were applied to assess environmental correlates. The Family-Based Association Test was used to test genetic associations for 23 single nucleotide polymorphism (SNP) markers in 7 caries candidate genes on 333 Caucasian parent-child trios. We evaluated the associations between caries status and the level of both single and multiple SNPs (haplotype) respectively. Permutation procedure was performed for correction of inflated type I errors due to multiple testing. Age, tooth-brushing frequency and water fluoride level were significantly correlated to at least one carious score. Caries on pit and fissure surfaces was substantially higher than on smooth surfaces (61 vs. 39%). SNPs in three genes (DSPP, KLK4 and AQP5) showed consistent associations with protection against caries. Of note, KLK4 and AQP5 were also highlighted by subsequent haplotype analysis. Our results support the concept that genes can modify the susceptibility of caries in children. Replication analysis in independent cohorts is highly needed in order to verify the validity of our findings.

Dietary Patterns and Risk of a New Carious Lesion Postpartum: A Cohort Study.

Dental caries (cavities), one of the most common infectious diseases, is caused by a number of factors. Oral microbes, dietary practices, sociodemographic factors, and dental hygiene all inform caries risk. Assessing the impact of diet is complicated as individuals eat foods in combinations, and the interactions among the foods may alter caries risk. Our study aimed to prospectively assess the association between dietary patterns and caries risk in the postpartum period, a potentially sensitive period for caries development. We analyzed in-person dental assessments and telephone food frequency questionnaires (FFQs) from 879 Caucasian women participating in the Center for Oral Health Research in Appalachia Cohort 2 (COHRA2) that were collected biannually for up to 6 y. One-week recall of food intake frequency was assessed using a Likert scale. We used principal component analysis to summarize the FFQ data; the top 2 components described 15% and 12% of the variance in FFQ data. The first component was characterized by high consumption of fruits and vegetables, while the second component was heavily influenced by desserts and crackers. We used a modified Poisson model to predict the risk of an increase in the number of decayed, missing, and filled teeth in the postpartum period by 1) dietary patterns and 2) individual foods and beverages at the previous study visit, after controlling for other known risk factors, including history of carious lesions. Eating a dietary pattern high in desserts and crackers was associated with a 20% increase in the number of decayed, missing, and filled teeth in the postpartum period (95% confidence interval, 1.03-1.39). However, this effect was attenuated among those who also consumed a dietary pattern high in fruits and vegetables. Dietary patterns should be considered when devising interventions aimed at preventing dental caries.

Plaque Microbiome in Caries-Active and Caries-Free Teeth by Dentition.

OBJECTIVE: Describe associations between dental caries and dental plaque microbiome, by dentition and family membership. METHODS: This cross-sectional analysis included 584 participants in the Center for Oral Health Research in Appalachia Cohort 1 (COHRA1). We sequenced the 16S ribosomal RNA gene (V4 region) of frozen supragingival plaque, collected 10 y prior, from 185 caries-active (enamel and dentinal) and 565 caries-free (no lesions) teeth using the Illumina MiSeq platform. Sequences were filtered using the R DADA2 package and assigned taxonomy using the Human Oral Microbiome Database. RESULTS: Microbiomes of caries-active and caries-free teeth were most similar in primary dentition and least similar in permanent dentition, but caries-active teeth were significantly less diverse than caries-free teeth in all dentition types. Streptococcus mutans had greater relative abundance in caries-active than caries-free teeth in all dentition types (P < 0.01), as did Veillonella dispar in primary and mixed dentition (P < 0.01). Fusobacterium sp. HMT 203 had significantly higher relative abundance in caries-free than caries-active teeth in all dentition types (P < 0.01). In a linear mixed model adjusted for confounders, the relative abundance of S. mutans was significantly greater in plaque from caries-active than caries-free teeth (P < 0.001), and the relative abundance of Fusobacterium sp. HMT 203 was significantly lower in plaque from caries-active than caries-free teeth (P < 0.001). Adding an effect for family improved model fit for Fusobacterium sp. HMT 203 but notS. mutans. CONCLUSIONS: The diversity of supragingival plaque composition from caries-active and caries-free teeth changed with dentition, but S. mutans was positively and Fusobacterium sp. HMT 203 was negatively associated with caries regardless of dentition. There was a strong effect of family on the associations of Fusobacterium sp. HMT 203 with the caries-free state, but this was not true for S. mutans and the caries-active state. KNOWLEDGE TRANSFER STATEMENT: Patients' and dentists' concerns about transmission of bacteria within families causing caries should be tempered by the evidence that some shared bacteria may contribute to good oral health.

Dental Caries Severity and Nutritional Status of Nigerian Preschool Children.

INTRODUCTION: Malnutrition in children is one of the most prevalent global health challenges, and malnourished children have a higher risk of death from childhood diseases. Early childhood caries (ECC) is the most common chronic disease of childhood. Complications from ECC such as pain, loss of tooth/teeth, and infection can undermine a child's nutrition and growth. AIM: This study aims to evaluate the severity of decay, missing, and filled tooth (dmft) by nutritional status using the z scores of the anthropometric measurements: height for age (HFA), weight for age (WFA), weight for height (WFH), and body mass index for age (BMIA) among children with ECC in Nigeria. STUDY DESIGN: This is a cross-sectional study conducted in 5 local government areas (LGAs) in Lagos State, Nigeria. A multistage sampling technique was used. RESULTS: A total of 273 cases of ECC were included in the analyses (mean age 4.19 ± 0.96 y). Overall, the mean dmft was 3.04 ± 2.28, and most (96%) were accounted for by untreated decay. The distribution of dmft within the different z score categories of BMIA (<-3 = severely wasted, -2 to -3 = wasted, -2 to +2 = normal, +2 to +3 = overweight and >+3 = obese) showed the highest dmft scores among the combined severely wasted and wasted groups, lowest among children with normal z scores, and intermediate in the overweight and obese groups. There was a significant negative correlation between BMIA z score, WFH z score, and dmft (r = -0.181, P < 0.05 and r = -0.143, P < 0.05, respectively). However, the correlations between HFA z score, WFA z score, and dmft were positive but not significant (r = 0.048, P = 0.44 and r = 0.022, P = 0.77, respectively). CONCLUSION: Our study showed an increased severity of dental caries among severely wasted or wasted children with ECC compared to those of normal or overweight. KNOWLEDGE TRANSFER STATEMENT: The results from this study will raise awareness among clinicians and policy makers on the need for a primary prevention program for early childhood caries in countries with high burden of malnutrition and limited resources. Also, it will help draw the attention of clinicians to the caries status of malnourished children that can be managed to improve the nutritional outcomes.

Genome-wide Scan of Dental Fear and Anxiety Nominates Novel Genes.

Dental care-related fear and anxiety (DFA) is prevalent, affects oral health care utilization, and is related to poor oral health and decreased quality of life. In addition to learned and cultural factors, genetics is hypothesized to contribute to DFA. Therefore, we performed a genome-wide association study to identify genetic variants contributing to DFA. Adult and adolescent participants were from 4 cohorts (3 from the US-based Center for Oral Health Research in Appalachia, n = 1,144, 1,164, and 535, and the UK-based Avon Longitudinal Study of Parents and Children [ALSPAC], n = 2,078). Two self-report instruments were used to assess DFA: the Dental Fear Survey (US cohorts) and Corah's Dental Anxiety Scale (ALSPAC). Genome-wide scans were performed for the DFA total scores and subscale scores (avoidance, physiological arousal, fear of dental treatment-specific stimuli), adjusting for age, sex, educational attainment, recruitment site, and genetic ancestry. Results across cohorts were combined using meta-analysis. Heritability estimates for DFA total and subscale scores were similar across cohorts and ranged from 23% to 59%. The meta-analysis revealed 3 significant (P < 5E-8) associations between genetic loci and 2 DFA subscales: physiological arousal and avoidance. Nearby genes included NTSR1 (P = 3.05E-8), DMRTA1 (P = 4.40E-8), and FAM84A (P = 7.72E-9). Of these, NTSR1, which was associated with the avoidance subscale, mediates neurotensin function, and its deficiency may lead to altered fear memory in mice. Gene enrichment analyses indicated that loci associated with the DFA total score and physiological arousal subscale score were enriched for genes associated with severe and persistent mental health (e.g., schizophrenia) and neurocognitive (e.g., autism) disorders. Heritability analysis indicated that DFA is partly explained by genetic factors, and our association results suggested shared genetic underpinnings with other psychological conditions.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Opposition to Early Dental Visit by Dentists: A Qualitative Study on Mothers' Social Networks.

OBJECTIVES: To examine whether information that mothers received from dentists in their social network was consistent with professional recommendations for the first dental visit at age 1 y. METHODS: We performed a cross-sectional qualitative study on mothers in Pennsylvania and West Virginia from 2018 to 2020 to explore how their social networks influence their children's dental service utilization. In-person, semistructured interviews were conducted with 126 mothers of children ages 3 to 5 y. Qualitative data were transcribed, coded, and analyzed using NVivo 12. Two investigators analyzed data using grounded theory and the constant comparative method. RESULTS: Over half of mothers reported a professional relationship with a dentist as part of their social network on children's oral health. Mothers described the following themes: 1) mothers contacted dentists in their social network for child dental information and to schedule their child's first dental visit, 2) mothers described dentists' justifications for the timing of the first dental visit older than age 1 y, 3) mothers described the impact of the dentist declining to see her child, and 4) after the dentist declined to see her child, some mothers did not comply with the dentist's recommendation of delayed child dental visits because they were given alternative information that encouraged early dental visits. CONCLUSIONS: Our findings indicate a need for dentists to reinforce mothers' dental-seeking behavior for young children and adhere to recommendations on the age 1 dental visit. KNOWLEDGE TRANSFER STATEMENT: Qualitative data on mothers' social networks show that dentists play a key role in access to early dental visits, particularly when dentists decline to see the mother's child for visits.

Maternal Oral Health Influences Infant Salivary Microbiome.

Oral microbiomes vary in cariogenic potential; these differences may be established early in life. A major concern is whether mothers transmit cariogenic bacteria to their children. Here we characterize early salivary microbiome development and the potential associations of that development with route of delivery, breastfeeding, and mother's oral health, and we evaluate transmission of microbes between mother and child. We analyzed saliva and metadata from the Center for Oral Health Research in Appalachia. For this cohort study, we sequenced the V6 region of the 16S rRNA gene and used quantitative polymerase chain reaction to detect Streptococcus mitis, Streptococcus sobrinus, Streptococcus mutans, Streptococcus oralis, and Candida albicans in the saliva from mothers and their infants, collected at 2, 9, and 12 mo (Pennsylvania site) and 2, 12, and 24 mo (West Virginia site). Breastfed children had lower relative abundances of Prevotella and Veillonella. If mothers had decayed, missing, or filled teeth, children had greater abundances of Veillonella and Actinomyces. There was little evidence of maternal transmission of selected microbes. At 12 mo, children's microbiomes were more similar to other children's than to their mothers'. Infants' salivary microbiomes became more adult-like with age but still differed with mothers' microbiomes at 12 mo. There was little evidence supporting transmission of selected microbes from mothers to children, but risk of colonization was associated with tooth emergence. Children are likely to acquire cariogenic bacteria from a variety of sources, including foods and contact with other children and adults.

Association between Dental Anomalies and Orofacial Clefts: A Meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess whether individuals with nonsyndromic orofacial clefts (OCs) display a higher frequency of dental anomalies (DAs) when compared with individuals without OCs. METHODS: A literature search of indexed databases (PubMed, Cochrane, Web of Science, Embase, Scopus, and LILACS) was conducted without language restriction up to and including February 1, 2020. Cross-referencing was used to further identify articles. Several cleft teams across the United States and Europe were contacted to obtain unpublished data. The eligibility criteria were observational studies with original data that statistically compared individuals with OC without syndromes and those without OC on any type of DA in primary and/or permanent dentition. Random effects meta-analysis through the Mantel-Haenszel estimator was used to evaluate the association between OC and DA based on odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The literature search generated 933 records, and 75 full-text articles were reviewed. Twenty-six studies encompassing 15,213 individuals met the inclusion criteria. The meta-analysis revealed statistically significant associations between OC and agenesis (OR, 14.2; 95% CI, 9.4 to 21.3), supernumerary teeth (OR, 5.7; 95% CI, 3.3 to 9.7), developmental enamel defects (OR, 5.6; 95% CI, 3.5 to 9.0), microdontia (OR, 14.8; 95% CI, 4.0 to 54.6), peg-shaped anterior teeth (OR, 12.2; 95% CI, 3.6 to 41.2), taurodontism (OR, 1.7; 95% CI, 1.0 to 2.7), tooth malposition and/or transposition (OR, 5.6; 95% CI, 2.8 to 11.5), tooth rotation (OR, 3.2; 95% CI, 1.3 to 8.2), and tooth impaction (OR, 3.6; 95% CI, 1.1 to 12.2). The OR estimates of the reviewed studies exhibited significant heterogeneity (P < 0.0001). No association was observed between OC and fusion and/or gemination. CONCLUSION: Within the limitations of this study, the available evidence suggests that individuals with OCs are more likely to present with a range of DAs than their unaffected peers. KNOWLEDGE TRANSFER STATEMENT: The findings of the current review suggest that individuals with orofacial clefts (OCs) are more likely to present with a range of dental anomalies than their unaffected peers. Understanding the association between OCs and dental anomalies is essential in guiding clinicians during treatment-planning procedures and is important in raising our awareness of the possible need for future dental treatment for patients with OCs.

Genes and their effects on dental caries may differ between primary and permanent dentitions.

The importance of genetic factors in the genesis of dental caries of both primary and permanent dentitions is well established; however, the degree to which genes contribute to the development of dental caries, and whether these genes differ between primary and permanent dentitions, is largely unknown. Using family-based likelihood methods, we assessed the heritability of caries-related phenotypes for both children and adults in 2,600 participants from 740 families. We found that caries phenotypes in the primary dentition were highly heritable, with genes accounting for 54-70% of variation in caries scores. The heritability of caries scores in the permanent dentition was also substantial (35-55%, all p < 0.01), although this was lower than analogous phenotypes in the primary dentition. Assessment of the genetic correlation between primary and permanent caries scores indicated that 18% of the covariation in these traits was due to common genetic factors (p < 0.01). Therefore, dental caries in primary and permanent teeth may be partly attributable to different suites of genes or genes with differential effects. Sex and age explained much of the phenotypic variation in permanent, but not primary, dentition. Further, including pre-cavitated white-spot lesions in the phenotype definition substantially increased the heritability estimates for dental caries. In conclusion, our results show that dental caries are heritable, and suggest that genes affecting susceptibility to caries in the primary dentition may differ from those in permanent teeth. Moreover, metrics for quantifying caries that incorporate white-spot lesions may serve as better phenotypes in genetic studies of the causes of tooth decay.

Comparative whole-genome analysis of Streptococcus mutans isolates within and among individuals of different caries status.

INTRODUCTION: Genotypic analyses of Streptococcus mutans using fingerprinting methods depend on a few genetic loci being different but do not reveal the underlying genome-wide differences between strains. METHODS: We used comparative genomic hybridization (CGH) with 70-mer oligonucleotide microarrays containing open reading frames (ORFs) from S. mutans strain UA159 to examine the genetic diversity of 44 isolates from nine children selected from a local study population in Eastern Iowa. RESULTS: Unique strains (clones) within each child initially identified by arbitrary-priming polymerase chain reaction were confirmed by CGH. There was a wide range of variation in the hybridization patterns of the 1948 ORFs among the test isolates examined. Between 87 and 237 ORFs failed to give a positive signal among individual isolates. A total of 323 of the UA159 ORFs were absent from one or more of the test strains. These 323 variable genes seemed to be distributed across the entire UA159 genome and across all the predicted functional categories. CONCLUSION: This set of very close geographically and temporally collected S. mutans isolates had a degree of gene content variation as high as a previously examined global set of strains. Comparing the frequency of these variable genes, the majority of which have unknown function, among strains of different origins (i.e. different caries status) could help to determine their relevance in S. mutans cariogenicity.

Face shape of unaffected parents with cleft affected offspring: combining three-dimensional surface imaging and geometric morphometrics.

OBJECTIVE: Various lines of evidence suggest that face shape may be a predisposing factor for non-syndromic cleft lip with or without cleft palate (CL/P). In the present study, 3D surface imaging and statistical shape analysis were used to evaluate face shape differences between the unaffected (non-cleft) parents of individuals with CL / P and unrelated controls. METHODS: Sixteen facial landmarks were collected from 3D captures of 80 unaffected parents and 80 matched controls. Prior to analysis, each unaffected parent was assigned to a subgroup on the basis of prior family history (positive or negative). A geometric morphometric approach was utilized to scale and superimpose the landmark coordinate data (Procrustes analysis), test for omnibus group differences in face shape, and uncover specific modes of shape variation capable of discriminating unaffected parents from controls. RESULTS: Significant disparity in face shape was observed between unaffected parents and controls (p < 0.01). Notably, these changes were specific to parents with a positive family history of CL/P. Shape changes associated with CL/P predisposition included marked flattening of the facial profile (midface retrusion), reduced upper facial height, increased lower facial height, and excess interorbital width. Additionally, a sex-specific pattern of parent-control difference was evident in the transverse dimensions of the nasolabial complex. CONCLUSIONS: The faces of unaffected parents from multiplex cleft families displayed meaningful shape differences compared with the general population. Quantitative assessment of the facial phenotype in cleft families may enhance efforts to discover the root causes of CL/P.