Genetic influences on dentognathic morphology in the Jirel population of Nepal.

Patterns of genetic variation and covariation impact the evolution of the craniofacial complex and contribute to clinically significant malocclusions in modern human populations. Previous quantitative genetic studies have estimated the heritabilities and genetic correlations of skeletal and dental traits in humans and nonhuman primates, but none have estimated these quantitative genetic parameters across the dentognathic complex. A large and powerful pedigree from the Jirel population of Nepal was leveraged to estimate heritabilities and genetic correlations in 62 maxillary and mandibular arch dimensions, incisor and canine lengths, and post-canine tooth crown areas (N ≥ 739). Quantitative genetic parameter estimation was performed using maximum likelihood-based variance decomposition. Residual heritability estimates were significant for all traits, ranging from 0.269 to 0.898. Genetic correlations were positive for all trait pairs. Principal components analyses of the phenotypic and genetic correlation matrices indicate an overall size effect across all measurements on the first principal component. Additional principal components demonstrate positive relationships between post-canine tooth crown areas and arch lengths and negative relationships between post-canine tooth crown areas and arch widths, and between arch lengths and arch widths. Based on these findings, morphological variation in the human dentognathic complex may be constrained by genetic relationships between dental dimensions and arch lengths, with weaker genetic correlations between these traits and arch widths allowing for variation in arch shape. The patterns identified are expected to have impacted the evolution of the dentognathic complex and its genetic architecture as well as the prevalence of dental crowding in modern human populations.

Craniofacial growth and morphology among intersecting clinical categories.

Differential patterns of craniofacial growth are important sources of variation that can result in skeletal malocclusion. Understanding the timing of growth milestones and morphological change associated with adult skeletal malocclusions is critical for developing individualized orthodontic growth modification strategies. To identify patterns in the timing and geometry of growth, we used Bayesian modeling of cephalometrics and geometric morphometric analyses with a dense, longitudinal sample consisting of 15,407 cephalograms from 1,913 individuals between 2 and 31 years of age. Individuals were classified into vertical facial types (hyper-, normo-, hypo-divergent) and anteroposterior (A-P) skeletal classes (Class I, Class II, Class III) based on adult mandibular plane angle and ANB angle, respectively. These classifications yielded eight facial type-skeletal class categories with sufficient sample sizes to be included in the study. Four linear cephalometrics representing facial heights and maxillary and mandibular lengths were fit to standard double logistic models generating type-class category-specific estimates for age, size, and rate of growth at growth milestones. Mean landmark configurations were compared among type-class categories at four time points between 6 and 20 years of age. Overall, morphology and growth patterns were more similar within vertical facial types than within A-P classes and variation among A-P classes typically nested within variation among vertical types. Further, type-class-associated variation in the rate and magnitude of growth in specific regions identified here may serve as targets for clinical treatment of complex vertical and A-P skeletal malocclusion and provide a clearer picture of the development of variation in craniofacial form.

Estimating Craniofacial Growth Cessation: Comparison of Asymptote- and Rate-Based Methods.

OBJECTIVE: To identify differences between asymptote- and rate-based methods for estimating age and size at growth cessation in linear craniofacial measurements. DESIGN: This is a retrospective, longitudinal study. Five linear measurements were collected from lateral cephalograms as part of the Craniofacial Growth Consortium Study (CGCS). Four estimates of growth cessation, including 2 asymptote- (GCasym, GCerr) and 2 rate-based (GCabs, GC10%) methods, from double logistic models of craniofacial growth were compared. PARTICIPANTS: Cephalometric data from participants in 6 historic longitudinal growth studies were included in the CGCS. At least 1749 individuals (870 females, 879 males), unaffected by craniofacial anomalies, were included in all analyses. Individuals were represented by a median of 11 images between 2.5 and 31.3 years of age. RESULTS: GCasym consistently occurred before GCerr and GCabs consistently occurred before GC10% within the rate-based approaches. The ordering of the asymptote-based methods compared to the rate-based methods was not consistent across measurements or between males and females. Across the 5 measurements, age at growth cessation ranged from 13.56 (females, nasion-basion, GCasym) to 24.39 (males, sella-gonion, GCerr). CONCLUSIONS: Adolescent growth cessation is an important milestone for treatment planning. Based on our findings, we recommend careful consideration of specific definitions of growth cessation in both clinical and research settings since the most appropriate estimation method may differ according to patients' needs. The different methods presented here provide useful estimates of growth cessation that can be applied to raw data and to a variety of statistical models of craniofacial growth.

Geometric morphometric analysis of growth patterns among facial types.

INTRODUCTION: Extreme patterns of vertical facial divergence are of great importance to clinicians because of their association with dental malocclusion and functional problems of the orofacial complex. Understanding the growth patterns associated with vertical facial divergence is critical for clinicians to provide optimal treatment. This study evaluates and compares growth patterns from childhood to adulthood among 3 classifications of vertical facial divergence using longitudinal, lateral cephalograms from the Craniofacial Growth Consortium Study. METHODS: Participants (183 females, 188 males) were classified into 1 of 3 facial types on the basis of their adult mandibular plane angle (MPA): hyperdivergent (MPA >39°; n = 40), normodivergent (28° ≤ MPA ≤ 39°; n = 216), and hypodivergent (MPA <28°; n = 115). Each individual had 5 cephalograms between ages 6 and 20 years. A set of 36 cephalometric landmarks were digitized on each cephalogram. Landmark configurations were superimposed to align 5 homologous landmarks of the anterior cranial base and scaled to unit centroid size. Growth trajectories were calculated using multivariate regression for each facial type and sex combination. RESULTS: Divergent growth trajectories were identified among facial types, finding more similarities in normodivergent and hypodivergent growth patterns than either share with the hyperdivergent group. Through the use of geometric morphometric methods, new patterns of facial growth related to vertical facial divergence were identified. Hyperdivergent growth exhibits a downward rotation of the maxillomandibular complex relative to the anterior cranial base, in addition to the increased relative growth of the lower anterior face. Conversely, normodivergent and hypodivergent groups exhibit stable positioning of the maxilla relative to the anterior cranial base, with the forward rotation of the mandible. Furthermore, the hyperdivergent maxilla and mandible become relatively shorter and posteriorly positioned with age compared with the other groups. CONCLUSIONS: This study demonstrates how hyperdivergent growth, particularly restricted growth and positioning of the maxilla, results in a higher potential risk for Class II malocclusion. Future work will investigate growth patterns within each classification of facial divergence.

Bayesian approach to longitudinal craniofacial growth: The Craniofacial Growth Consortium Study.

Early in the 20th century, a series of studies were initiated across North America to investigate and characterize childhood growth. The Craniofacial Growth Consortium Study (CGCS) combines craniofacial records from six of those growth studies (15,407 lateral cephalograms from 1,913 individuals; 956 females, 957 males, primarily European descent). Standard cephalometric points collected from the six studies in the CGCS allows direct comparison of craniofacial growth patterns across six North American locations. Three assessors collected all cephalometric points and the coordinates were averaged for each point. Twelve measures were calculated from the averaged coordinates. We implemented a multilevel double logistic equation to estimate growth trajectories fitting each trait separately by sex. Using Bayesian inference, we fit three models for each trait with different random effects structures to compare differences in growth patterns among studies. The models successfully identified important growth milestones (e.g., age at peak growth velocity, age at cessation of growth) for most traits. In a small number of cases, these milestones could not be determined due to truncated age ranges for some studies and slow, steady growth in some measurements. Results demonstrate great similarity among the six growth studies regarding craniofacial growth milestone estimates and the overall shape of the growth curve. These similarities suggest minor variation among studies resulting from differences in protocol, sample, or possible geographic variation. The analyses presented support combining the studies into the CGCS without substantial concerns of bias. The CGCS, therefore, provides an unparalleled opportunity to examine craniofacial growth from childhood into adulthood.

Genetic correlations in the rhesus macaque dentition.

Quantitative genetic analyses can indicate how complex traits respond to natural selection by demonstrating the genetic relationships between features that constrain their evolution. Genetic correlations between dental measurements have been estimated previously in baboons, humans, and tamarins and indicate variable patterns of modularity by tooth type across these taxa. Here, heritabilities of, and genetic correlations between, linear dental measurements were estimated from the Cayo Santiago rhesus macaques (Macaca mulatta). Relationships between the genetic correlation matrix and matrices designed to test hypotheses of modularity by tooth type, region, function, and development were assessed using a random skewers approach. Dental measurements were found to be moderately to highly heritable, with 24 of 28 heritability estimates differing significantly (p < 0.05) from zero. Almost all genetic correlations between dental dimensions were positive. The genetic correlation matrix was most similar to a regionally modular matrix, with distinct anterior and postcanine tooth modules. This pattern is consistent with previous quantitative genetic analyses of baboons and previous phenotypic analyses of cercopithecoid primates. The existence of a genetic module for the canines and honing premolar was not supported. Ongoing selection pressures, rather than strong genetic constraints, are likely necessary to preserve functional relationships between the canines and honing premolar based on these findings. The genetic correlation matrix of the Cayo Santiago rhesus macaques mirrors patterns of phenotypic correlations observed for cercopithecoid primates broadly and demonstrates that genetic contributions to these patterns may be fairly stable over the course of cercopithecoid evolution. The quantitative genetic study of additional taxa will be necessary to determine whether the regional modularity of baboons and macaques, or the integrated pattern of humans and tamarins, is shared more broadly across primates.

Clinical implications of age-related change of the mandibular plane angle.

OBJECTIVE: To identify trajectories of ontogenetic change in the mandibular plane angle (MPA) and to describe the influence of sex and other factors on MPA during growth. SETTING/SAMPLE: The data consisted of 7026 MPA measurements from lateral cephalographs representing longitudinal series from ages 6 to 21 for 728 individuals from the Craniofacial Growth Consortium Study (CGCS). MATERIALS AND METHODS: Facial type was determined from MPA for each assessment, with the assessment closest to age 18 representing the adult facial type. The sample includes 366 males and 362 females, each with between 2 and 15 cephalographs. The mean number of cephalographs per individual is 10. Variation in childhood MPA (earliest assessment between 6 and 9 years of age) and adult MPA (closest assessment to age 18 between 15 and 21 years of age), and change in MPA from childhood to adulthood were compared by sex and adult facial type using ANOVA and post hoc t tests. RESULTS: Mandibular plane angle decreased from childhood to adulthood in 92% of males and 81% of females, yet increased in 36% of males and 50% of females with the hyper-divergent adult facial type. Childhood MPA and overall change in MPA were significantly different by adult facial type. CONCLUSIONS: Adult facial type is associated with differences in childhood MPA and change in MPA during growth. There are multiple ontogenetic pathways by which an individual can achieve a normo-divergent adult facial type, and an individual's childhood MPA does not necessarily correspond to his or her adult facial type.

Genetic correlations in the dental dimensions of Saguinus fuscicollis.

OBJECTIVES: The objectives of this study are to describe genetic correlations between dental dimensions in a platyrrhine primate, to assess whether the brown-mantled tamarin dentition exhibits genetic modularity by tooth type, and to discuss the relationship between body size reduction and the genetic architecture of dental traits. MATERIALS AND METHODS: Genetic correlations were estimated for linear dental measurements, estimated crown areas, and measures of relative premolar and molar size from 302 individuals, using a pedigree of 386 individuals, with maximum likelihood variance decomposition in SOLAR. RESULTS: Genetic correlation estimates indicate strong genetic integration in the dentition of brown-mantled tamarins, with little evidence of modularity by tooth type, within and between the maxilla and mandible. The relative molar size variable hypothesized to be genetically patterned in baboons is not significantly heritable, and relative premolar size does not meet the criteria to be considered genetically patterned in this population. DISCUSSION: These results demonstrate variation in the pattern of genetic correlations between dental dimensions in primates, providing evidence of evolution of the genetic architecture in the callitrichine lineage. Genetic integration of dental dimensions without modularity by tooth type, as demonstrated here, is expected to constrain dental evolution in ways that modularity would not. The role of body size reduction in the callitrichine lineage in the evolution of the genetic architecture of the dentition is discussed. Quantitative genetic analyses of dental dimensions in more primate populations will provide greater evidence of variation and evolution in the genetic architecture underlying primate dental morphology.

Genetic contributions to dental dimensions in brown-mantled tamarins (Saguinus fuscicollis) and rhesus macaques (Macaca mulatta).

OBJECTIVES: The use of dental metrics in phylogenetic reconstructions of fossil primates assumes variation in tooth size is highly heritable. Quantitative genetic studies in humans and baboons have estimated high heritabilities for dental traits, providing a preliminary view of the variability of dental trait heritability in nonhuman primate species. To expand upon this view, the heritabilities and evolvabilities of linear dental dimensions are estimated in brown-mantled tamarins (Saguinus fuscicollis) and rhesus macaques (Macaca mulatta). MATERIALS AND METHODS: Quantitative genetic analyses were performed on linear dental dimensions collected from 302 brown-mantled tamarins and 364 rhesus macaques. Heritabilities were estimated in SOLAR using pedigrees from each population, and evolvabilities were calculated manually. RESULTS: Tamarin heritability estimates range from 0.19 to 0.99, and 25 of 26 tamarin estimates are significantly different from zero. Macaque heritability estimates range from 0.08 to 1.00, and 25 out of 28 estimates are significantly different from zero. DISCUSSION: Dental dimensions are highly heritable in captive brown-mantled tamarins and free-ranging rhesus macaques. The range of heritability estimates in these populations is broadly similar to those of baboons and humans. Evolvability tends to increase with heritability, although evolvability is high relative to heritability in some dimensions. Estimating evolvability helps to contextualize differences in heritability, and the observed relationship between evolvability and heritability in dental dimensions requires further investigation.