Limb development genes underlie variation in human fingerprint patterns.

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.

Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts.

Enamel hypoplasia causes reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. A genome-wide association of enamel hypoplasia was performed in multiple cohorts, overall comprising 7,159 individuals ranging in age from 7-82 years. Mixed-models were used to test for genetic association while simultaneously accounting for relatedness and genetic population structure. Meta-analysis was then performed. More than 5 million single-nucleotide polymorphisms were tested in individual cohorts. Analyses of the individual cohorts and meta-analysis identified association signals close to genome-wide significance (P < 510-8), and many suggestive association signals (510-8 < P < 510-6) near genes with plausible roles in tooth/enamel development. The strongest association signal (P = 1.5710-9) was observed near BMP2K in one of the individual cohorts. Additional suggestive signals were observed near genes with plausible roles in tooth development in the meta-analysis, such as SLC4A4 which can influence enamel hypoplasia. Additional human genetic studies are needed to replicate these results and functional studies in model systems are needed to validate our findings.

The Influence of Sex and Ancestry on Three-Dimensional Palate Shape.

ABSTRACT: Modern human palate shape has been reported to vary by sex and ancestry, but limitations in the methods used to quantify shape and in population coverage have led to inconsistent findings. In the present study, the authors aim to characterize the effects of sex and ancestry on normal-range three-dimensional palate shape through landmark-based morphometrics.Three-dimensional digital dental casts were obtained and landmarked from 794 adults of European (n = 429), African (n = 295), and East Asian (n = 70) ancestry. Principal component analysis was conducted to identify patterns of shape variation present in our cohort, and canonical variates analysis was performed to test for shape differences between sexes and ancestries.Principal component analysis showed that 3 principal components, explaining 76.52% of variance, linked higher palatal vault with either a relative reduction in anteroposterior or mediolateral dimensions. Canonical variates analysis showed that males had wider and shorter palates with more posteriorly located maximum vault depth than females. Individuals of African ancestry, having higher vaults with more posteriorly located maximal depths, also had wider and shorter palates, whereas individuals of European ancestry had narrower and longer palates with more anteriorly located maximum vault depths. Individuals of East Asian ancestry showed the shallowest vaults.It was found that both sex and ancestry influence palate shape, suggesting a possible genetic component underlying this variation. Additionally, our findings indicate that vault height tends to co-vary with anteroposterior or mediolateral dimensions. Further investigation of these morphological patterns may shed light on possible links to common congenital anomalies such as orofacial clefting.

Parents of Children With Nonsyndromic Orofacial Clefting Show Altered Palate Shape.

OBJECTIVE: The unaffected relatives of individuals with nonsyndromic orofacial clefts have been shown to exhibit subtle craniofacial differences compared with the general population. Here, we investigate whether these morphological differences extend to the shape of the palate. DESIGN: We conducted a geometric morphometric analysis to compare palate shape in the clinically unaffected parents of children with nonsyndromic cleft lip with or without cleft palate and adult controls of European, Asian, and African ancestry. We conducted pairwise group comparisons using canonical variates analysis, and then confirmed and characterized findings of shape differences using Euclidean distance matrix analysis. RESULTS: Significant differences in palate shape were detected in unaffected mothers (but not fathers) compared to demographically matched controls. The differences in shape were ancestry-specific; mothers of Asian-derived and African-derived ancestry showed wider and shorter palates with higher posterior palatal vaults, while mothers of European-derived ancestry showed narrower palates with higher anterior palatal vaults. CONCLUSIONS: Our findings suggest that altered palate shape is a subclinical phenotypic feature, which may be indicative of elevated orofacial cleft risk. The risk phenotype varied by sex and ancestry, suggesting possible etiologic heterogeneity among demographic groups. Understanding the genetic basis of these informative palate shape traits may reveal new genes and pathways relevant to nonsyndromic orofacial clefting.

Genome-Wide Association Study (GWAS) of dental caries in diverse populations.

BACKGROUND: Dental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent. METHODS: The aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18-60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification. RESULTS: We identified several suggestive loci (5 × 10-8 < P < 5 × 10-6) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis. CONCLUSION: The results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.

A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3.

Cleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met [c.1361C>T]; rs41268753; p = 4.08 × 10(-9)) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR = 8.3, 95% CI 4.1-16.8; OR = 2.16, 95% CI 1.43-3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis.

Transmission of dental fear from parent to adolescent in an Appalachian sample in the USA.

BACKGROUND: Dental fear/anxiety is associated with numerous negative outcomes. State dental fear is known to be transmitted from parents to their children in the dental setting, but it is not known how trait fear/anxiety might be shared between parents and offspring long term, and especially for adolescents. AIM: This study aimed to: (a) compare dental fear levels of adolescents and their parents; (b) predict adolescent dental fear based on demographic variables, fear of pain, and parental dental fear; and, (c) determine relative contributions of mothers' and fathers' dental fear to adolescent fear. DESIGN: In this cross-sectional study, the Dental Fear Survey and Fear of Pain Questionnaire-9 were administered to 350 adolescents (age range 11-17) and 515 of their parents, with t test and ANOVA used to calculate between-group differences; multiple linear regression was used to predict adolescent fear from parent fear. RESULTS: Adolescents' dental fear was predicted by their own fear of pain and their parents' dental fear, but not their parents' fear of pain nor their own age or gender. When considered together, fathers' but not mothers' dental fear predicted adolescents' dental fear. CONCLUSIONS: Parents' fears/anxieties about dentistry are associated with adolescents' dental fear in a manner suggestive of intergenerational transmission.

A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10-8), and 19q13 near RHPN2, a gene involved in organizing the actin cytoskeleton (P = 4.17 × 10-8). Other regions reaching genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and 17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group revealed a novel association with a region on 17q23 (P = 2.92 × 10-8) among individuals with European ancestry. This region included several promising candidates including TANC2, an oncogene required for development, and DCAF7, a scaffolding protein required for craniofacial development. In the Central and South American ancestry group, significant associations with loci previously identified in Asian or European ancestry groups reflected their admixed ancestry. In summary, we have identified novel CL/P risk loci and suggest new genes involved in craniofacial development, confirming the highly heterogeneous etiology of OFCs.

Effects of Specimen Collection Methodologies and Storage Conditions on the Short-Term Stability of Oral Microbiome Taxonomy.

UNLABELLED: Community profiling of the oral microbiome requires the recovery of quality sequences in order to accurately describe microbial community structure and composition. Our objective was to assess the effects of specimen collection method, storage medium, and storage conditions on the relative abundance of taxa in saliva and plaque identified using 16S rRNA genes. We also assessed short-term changes in taxon composition and relative abundance and compared the salivary and dental plaque communities in children and adults. Over a 2-week period, four successive saliva and dental plaque specimens were collected from four adults with no dental decay (108 samples), and two successive specimens were collected from six children with four or more erupted teeth (48 samples). There were minimal differences in community composition at the phylum and operational taxonomic unit levels between dental plaque collection using a scaler and collection using a CytoSoft brush. Plaque samples stored in OMNIgene medium showed higher within-sample Shannon diversity, were compositionally different, and were more similar to each other than plaque stored in liquid dental transport medium. Saliva samples stored in OMNIgene recovered similar communities for at least a week following storage at room temperature. However, the microbial communities recovered from plaque and saliva stored in OMNIgene were significantly different in composition from their counterparts stored in liquid dental transport medium. Dental plaque communities collected from the same tooth type over four successive visits from the same adult did not significantly differ in structure or composition. IMPORTANCE: Large-scale epidemiologic studies require collection over time and space, often with multiple teams collecting, storing, and processing data. Therefore, it is essential to understand how sensitive study results are to modest changes in collection and storage protocols that may occur with variation in personnel, resources available at a study site, and shipping requirements. The research presented in this paper measures the effects of multiple storage parameters and collection methodologies on the measured ecology of the oral microbiome from healthy adults and children. These results will potentially enable investigators to conduct oral microbiome studies at maximal efficiency by guiding informed administrative decisions pertaining to the necessary field or clinical work.

Nasolabial fold discontinuity during speech as a possible extended cleft phenotype.

Objective : This exploratory research sought to extend the cleft phenotype by identifying movement-related soft tissue appearance changes in the midfacial region in individuals with cleft lip/palate or those with genetic susceptibility to cleft lip/palate (unaffected relatives). The cleft phenotype (clinically identified orofacial cleft or subclinical orbicularis oris defect) was hypothesized to be associated with movement related appearance changes in the midfacial region, e.g., with furrowing and dimpling during speech. Design : Changes in the appearance of skin in the midfacial region, including a newly identified phenotypic feature, nasolabial fold (NLF) discontinuity, were described and compared across groups. Participants : Individuals with cleft lip (n  =  42), unaffected relatives of persons with a cleft (n  =  57) and healthy controls (n  =  41) were compared. Results : Frequencies of NLF discontinuity differed across cleft, relative, and control groups. NLF discontinuities were observed more frequently in individuals with a cleft phenotype (overt cleft or previously identified orbicularis oris muscle defect) than in those with no underlying muscular defect (Fisher exact test, P  =  .014). Conclusion : Results suggest that the appearance of facial soft tissue during movement of the midface is moderated at least in part by underlying cleft risk factors, indicating certain facial movements as candidate physical markers for extension of the cleft phenotype.

Maternal factors and risk of early childhood caries: A prospective cohort study.

OBJECTIVE: To evaluate the associations between time-varying factors (mother's oral health, oral hygiene, smoking habits, diet, food insecurity and stress) socioeconomic factors (mother's employment, marital status, household income, insurance status, household size) and medical history on children's risk of developing a carious lesion in the first 3 years of life. METHODS: Longitudinal data from the Center for Oral Health Research in Appalachia Cohort Two (COHRA2) were analysed. Pregnant women ≥18 years in the USA were recruited during pregnancy; all consenting women delivering at term and their babies had regular dental assessments and complete in-person surveys and telephone interviews regarding sociodemographic factors, medical and dental history, and oral health behaviours. RESULTS: In a logistic regression model adjusting for covariates, children whose mother had two or more prior pregnancies, smoked cigarettes post-partum, or had a recent unfilled carious lesion were at least twice as likely to experience a dental lesion by the three-year visit. The magnitude of these associations varied by maternal education and state of residence. CONCLUSIONS: Untreated maternal decay but not maternal oral hygiene or diet were associated with cumulative risk of childhood caries by age three but were modified by maternal education and state of residence. Addressing structural and behavioural issues that reduce use of restorative dental care are needed to prevent the adverse impacts associated with early childhood caries.

Food insecurity and consumption of cariogenic foods in mothers and their two-year-old children in Appalachia.

OBJECTIVES: To describe the association between household food insecurity and intake of cariogenic foods that increase risk of dental caries. METHODS: Cross-sectional analysis of 842 mothers in Appalachia and their children participating in the Center for Oral Health Research Cohort 2 between 2011 and 2017 when their children were ~ 24 months of age. Mothers completed a telephone interview regarding cariogenic food consumption and food insecurity. Associations between food insecurity and daily food intake were adjusted for education, income, state residence, and daily snacking. RESULTS: After adjustment for household income, state residence, daily snacking, and maternal education, mothers from moderately/severely food insecure households drank on average ½ more sugar-sweetened beverage servings per day (p = 0.005) and children drank almost 1/3 servings more (p = 0.006). Further, mothers and children from moderately/severely food insecure households had lower, but not statistically significant, daily average consumption of vegetables (mothers: 1/5 less of a vegetable serving per day, children: ~1/10 less) and fruits (mothers: 1/5 less of a fruit serving per day, children: ~ 1/10 les) and elevated consumption of sweets (mothers: ~ 1/25 more sweet servings per day, children: ~ 2/25 more); differences based on state residence were noted. CONCLUSIONS: Food insecurity is associated with higher consumption of foods that increase risk of dental caries, but this association is modified by maternal education, income, and state residence. Food insecurity, and its socioeconomic determinants, should be considered when designing and implementing interventions to prevent dental caries.

Potential risk factors and genetic variants associated with dental caries incidence in Appalachia using genome-wide survival analysis.

OBJECTIVE: The aim of this study was to identify the potential risk factors and genetic variants associated with dental caries incidence using survival analysis. METHODS: The Center for Oral Health Research in Appalachia recruited and prospectively followed pregnant women and their children. A total of 909 children followed from birth for up to 7 years were included in this study. Annual intra-oral examinations were performed to assess dental caries experience including the approximate time to first caries incidence in the primary dentition. Cox proportional hazards models were used to assess the associations of time to first caries incidence with self-reported risk factors and 4.9 million genetic variants ascertained using a genome-wide genotyping array. RESULTS: A total of 196 of 909 children (21.56%) had their first primary tooth caries event during follow-up. Household income, home water source, and mother's educational attainment were significantly associated with time to first caries incidence in the stepwise Cox model. The heritability (i.e., proportion of variance explained by genetics) of time to first caries was 0.54. Though no specific genetic variants were associated at the genome-wide significance level (P < 5E-8), we identified 14 loci at the suggestive significance level (5E-8 < P < 1E-5), some of which were located within or near genes with plausible biological functions in dental caries. CONCLUSION: Our findings indicate that household income, home water source, and mother's educational attainment are independent risk factors for dental caries incidence. We nominate several suggestive loci for further investigation.

Mutations in BMP4 are associated with subepithelial, microform, and overt cleft lip.

Cleft lip with or without cleft palate (CL/P) is a complex trait with evidence that the clinical spectrum includes both microform and subepithelial lip defects. We identified missense and nonsense mutations in the BMP4 gene in 1 of 30 cases of microform clefts, 2 of 87 cases with subepithelial defects in the orbicularis oris muscle (OOM), 5 of 968 cases of overt CL/P, and 0 of 529 controls. These results provide confirmation that microforms and subepithelial OOM defects are part of the spectrum of CL/P and should be considered during clinical evaluation of families with clefts. Furthermore, we suggest a role for BMP4 in wound healing.

Early Childhood Diet in Relation to Toddler Nighttime Sleep Duration Trajectories.

The objective of this study was to evaluate whether dietary habits at age 2 associate with sleep duration trajectories through age 5 in children from north and central Appalachia. A total of 559 children from the Center for Oral Health Research in Appalachia (COHRA) cohort 2 were followed via caregiver phone interviews up to six times between ages 2 and 5. Exposures included data from the year 2 interview: sleep habits, household and demographic characteristics, meal patterns and consumption frequencies of fruits, vegetables, water, juice, milk, and soda. Sleep duration trajectories were identified using group-based trajectory models from ages 2 to 5. Three distinct nightly sleep duration trajectories were identified: short, increasing duration (4.5% of the study population); steady, 9 h of sleep (37.3%); and longer, slightly decreasing sleep duration (58.2%). Using multinomial logistic models that accounted for confounders, children with consistent meal patterns (i.e., meals and snacks at same time every day) and with higher fruit and vegetable consumption were more likely to follow the longer duration sleep trajectory compared to the steady sleep trajectory. In contrast, children who drank milk more frequently at age 2 were less likely to be in the longer duration sleep trajectory than the steady sleep trajectory.

Oral health and related risk indicators in north-central Appalachia differ by rurality.

OBJECTIVES: This cross-sectional study assessed differences in oral health and related behaviours and risk indicators by rurality in a north-central Appalachian population using the Andersen behavioural model as a conceptual framework. METHODS: Participants were residents aged 18-59 years (n = 1311) from the Center for Oral Health Research in Appalachia, selected according to a household-based sampling strategy. Rural-Urban Continuum codes (RUC) corresponding to the participants' residences were used to classify participants as rural or urban. Mixed models were used to test rural-urban differences in measures of oral health, related behaviours, and need, enabling, and predisposing risk indicators. Models were adjusted for sociodemographic variables: age, sex, race, income, perceived socioeconomic status, educational attainment and dental insurance. RESULTS: Rural residents had poorer oral health overall, with fewer sound teeth (ß = -1.79), more dental caries (ß = 0.27) and higher rates of edentulism (5.2% vs 2.8%). Differences also were observed for dental care utilization and perceived barriers to care. Rural residents were less likely to attend dental visits as often as needed (26.9% vs 42.8%) and were more prone to seek care only after experiencing a dental problem (64.3% vs 43.9%). Rural residents also were more likely to report high costs (89% vs 62.6%) as a major reason for not having dental visits. Rural-urban differences for some oral health characteristics and behaviours could be explained by sociodemographic characteristics, whereas others could not. CONCLUSIONS: This study revealed rural-urban differences in risk indicators and oral health outcomes in north-central Appalachia. Many of these differences were explained, completely or partly, by sociodemographic factors.

Predictors of use of dental care by children in north-central Appalachia in the USA.

Use of dental services in childhood, especially preventive care, is associated with many important oral health outcomes throughout life. The Andersen behavioral model of healthcare utilization posits that predisposing characteristics, enabling resources, and need factors predict utilization in oral and other healthcare domains. Inequities that produce lower utilization of dental services in north-central Appalachia have been documented in comparison to the USA generally. Additionally, within Appalachia, there are disparities, such as those across different states related to varying public policies and resources supporting healthcare. Predictors of dental utilization in Appalachia have been a focus in adults, but less so in children. The aim of the current study was to understand predictors of dental utilization in children in north-central Appalachia in order to inform future research about how to intervene to address these disparities. In this study, there were 1,178 children, ages 1 through 10 years, from selected representative counties in West Virginia and Pennsylvania, along with a parent/caregiver, who were part of the Center for Oral Health Research in Appalachia (COHRA1) cohort. Use of dental services by their child was indicated by parents/caregivers, who also reported on sociodemographic, dental care-related anxiety and fear, and values and attitudes associated with oral healthcare. Results indicated that use of professional dental services by children was related to child age, dental anxiety and fear, and parental oral health values and attitudes. Older children in this age group, those who evidenced more dental care-related anxiety and fear, and whose parent/caregiver placed higher value on oral health and healthcare for themselves, were more likely to have had a dental visit in the past year.

Multivariate GWAS of Structural Dental Anomalies and Dental Caries in a Multi-Ethnic Cohort.

Odontogenesis is a complex process, where disruption can result in dental anomalies and/or increase the risk of developing dental caries. Based on previous studies, certain dental anomalies tend to co-occur in patients, suggesting that these traits may share common genetic and etiological components. The main goal of this study was to implement a multivariate genome-wide association study approach to identify genetic variants shared between correlated structural dental anomalies and dental caries. Our cohort (N = 3,579) was derived from the Pittsburgh Orofacial Clefts Study, where multiple dental traits were assessed in both the unaffected relatives of orofacial cleft (OFC) cases (n = 2,187) and unaffected controls (n = 1,392). We identified four multivariate patterns of correlated traits in this data: tooth agenesis, impaction, and rotation (AIR); enamel hypoplasia, displacement, and rotation (HDR); displacement, rotation, and mamelon (DRM); and dental caries, tooth agenesis and enamel hypoplasia (CAH). We analyzed each of these four models using genome-wide multivariate tests of association. No genome-wide statistically significant results were found, but we identified multiple suggestive association signals (P < 10-5) near genes with known biological roles during tooth development, including ADAMTS9 and PRICKLE2 associated with AIR; GLIS3, WDR72, and ROR2 associated with HDR and DRM; ROBO2 associated with DRM; BMP7 associated with HDR; and ROBO1, SMAD2, and MSX2 associated with CAH. This is the first study to investigate genetic associations for multivariate patterns of correlated dental anomalies and dental caries. Further studies are needed to replicate these results in independent cohorts.

Co-occurrence of yeast, streptococci, dental decay, and gingivitis in the post-partum period: results of a longitudinal study.

Objective: The interactions between yeast and streptococci species that lead to dental decay and gingivitis are poorly understood. Our study describes these associations among a cohort of 101 post-partum women enrolled in the Center for Oral Health Research in Appalachia, 2012-2013. Methods: All eligible women without dental caries were included (n = 21) and the remainder were randomly sampled to represent the total number of decayed, missing, and filled teeth (DMFT) at enrollment. We used amplicon sequencing and qPCR of saliva from 2, 6, 12 and 24 visits to determine microbiome composition. Results: Active decay and generalized gingivitis were strongly predictive of each other. Using adjusted marginal models, Candida albicans and Streptococcus mutans combined were associated with active decay (OR = 3.13; 95% CI 1.26, 7.75). However, C. albicans alone (OR = 2.33; 95% CI: 0.81, 6.75) was associated with generalized gingivitis, but S. mutans alone was not (OR = 0.55; 95% CI: 0.21, 1.44). Models including microbiome community state types (CSTs) showed CSTs positively associated with active decay were negatively associated with generalized gingivitis. Discussion: C. albicans is associated with active decay and generalized gingivitis, but whether one or both are present depends on the structure of the co-existing microbial community.

Individuals with nonsyndromic orofacial clefts have increased asymmetry of fingerprint patterns.

Dermatoglyphic patterns on the fingers often differ in syndromes and other conditions with a developmental component, compared to the general population. Previous literature on the relationship between orofacial clefts-the most common craniofacial birth defect in humans-and dermatoglyphics is inconsistent, with some studies reporting altered pattern frequencies and/or increased asymmetry and others failing to find differences. To investigate dermatoglyphics in orofacial clefting, we obtained dermatoglyphic patterns in a large multiethnic cohort of orofacial cleft cases (N = 367), their unaffected family members (N = 836), and controls (N = 299). We categorized fingerprint pattern types from males and females who participated at five sites of the Pittsburgh Orofacial Cleft study (Hungary, United States of America (Pennsylvania, Texas), Spain, and Argentina). We also calculated a pattern dissimilarity score for each individual as a measure of left-right asymmetry. We tested for group differences in the number of arches, ulnar and radial loops, and whorls on each individual's hands, and in the pattern dissimilarity scores using ANOVA. After taking sex and site differences into account, we did not find any significant pattern count differences between cleft and non-cleft individuals. Notably, we did observe increased pattern dissimilarity in individuals with clefts, compared to both their unaffected relatives and controls. Increased dermatoglyphic pattern dissimilarity in individuals with nonsyndromic orofacial clefts may reflect a generalized developmental instability.