Spatially dense 3D facial heritability and modules of co-heritability in a father-offspring design

Introduction: The human face is a complex trait displaying a strong genetic component as illustrated by various studies on facial heritability. Most of these start from sparse descriptions of facial shape using a limited set of landmarks. Subsequently, facial features are preselected as univariate measurements or principal components and the heritability is estimated for each of these features separately. However, none of these studies investigated multivariate facial features, nor the co-heritability between different facial features. Here we report a spatially dense multivariate analysis of facial heritability and co-heritability starting from data from fathers and their children available within ALSPAC. Additionally, we provide an elaborate overview of related craniofacial heritability studies. Methods: In total, 3D facial images of 762 father-offspring pairs were retained after quality control. An anthropometric mask was applied to these images to establish spatially dense quasi-landmark configurations. Partial least squares regression was performed and the (co-)heritability for all quasi-landmarks (∼7160) was computed as twice the regression coefficient. Subsequently, these were used as input to a hierarchical facial segmentation, resulting in the definition of facial modules that are internally integrated through the biological mechanisms of inheritance. Finally, multivariate heritability estimates were obtained for each of the resulting modules. Results: Nearly all modular estimates reached statistical significance under 1,000,000 permutations and after multiple testing correction (p ≤ 1.3889 × 10-3), displaying low to high heritability scores. Particular facial areas showing the greatest heritability were similar for both sons and daughters. However, higher estimates were obtained in the former. These areas included the global face, upper facial part (encompassing the nasion, zygomas and forehead) and nose, with values reaching 82% in boys and 72% in girls. The lower parts of the face only showed low to moderate levels of heritability. Conclusion: In this work, we refrain from reducing facial variation to a series of individual measurements and analyze the heritability and co-heritability from spatially dense landmark configurations at multiple levels of organization. Finally, a multivariate estimation of heritability for global-to-local facial segments is reported. Knowledge of the genetic determination of facial shape is useful in the identification of genetic variants that underlie normal-range facial variation

골격성 I급과 II급 유형을 가지는 쌍둥이의 얼굴 골격과 치열 특징의 유전율 차이에 관한 연구

학위논문(박사) -- 서울대학교대학원 : 치의학대학원 치의과학과, 2021.8. 김우리.Objective: To investigate differences in the heritability of skeletodental characteristics between skeletal Class I and Class II twin pairs. Methods: Forty Korean adult twin pairs were divided into Class I group (0°≤ANB≤4°; mean age, 40.7 years-old) and Class II group (ANB>4°; mean age, 43.0 years-old). Each group comprised 14 monozygotic and 6 dizygotic pairs. 33 cephalometric variables were measured using lateral cephalograms. Craniofacial structures were divided into the anteroposterior, vertical, dental, mandible, and cranial base characteristics. The ACE model was used to calculate heritability (A>0.7 indicates high heritability). Then, principal components analysis (PCA) was performed. Results: In the anteroposterior characteristics, high A values were observed for numerous variables in Class I group and for SNB and facial angle in Class II group. In the vertical characteristics, high A values were observed for FH-PP and PP-MP in Class I group and PP-MP, anterior and posterior facial height in Class II group. In the dental characteristics, high A values were observed only in Class I group. In the mandibular characteristics, CD-Gn and Ar-Go showed high A values in Class II group. The cranial base length variables (S-N, S-Ar, Ar-N) showed high A values in Class II group. The PCA demonstrated that Class I and Class II groups derived eight components with 88.3% cumulative explanation and seven components with 91.0% cumulative explanation, respectively. Conclusion: These results provide valuable information for growth prediction and planning of orthodontic and/or orthopedic treatment for Class I and Class II patients.목적: 본 연구는 골격성 I급 및 II급 환자의 두개안면 골격과 치열 특징의 유전율 차이를 연구하기 위해 시행되었다. 방법: 연구 대상은 한국인 성인 일란성 쌍둥이 (monozygotic twins, MZ) 와 성별이 동일한 이란성 쌍둥이(Dizygotic twins, DZ) 이었으며, 이들을 수평적 골격양상에 따라 골격성 I급 군(Class I group, 0°≤ANB≤4°, MZ 14쌍, DZ 6쌍)과 골격성 II급 군(Class II group, ANB>4°, MZ 14쌍, DZ ６쌍)으로 분류하였다. 측모두부계측 방사선사진 상에서 총 33개의 변수들을 계측하였고, 두개안면 구조물(craniofacial structures)을 전후방적, 수직적, 치열, 하악골, 두개저로 나누었다. ACE model을 사용하여 각 변수 및 두개안면 구조물의 유전율을 계산하였고, 유전율 값이 0.7을 초과하는 경우 높은 유전율을 갖는 것으로 판단하였다. 변수들에 대한 주성분분석 (principal component analysis)을 통해 각 군의 특성을 나타내는 주성분들을 추출하였고, 이 주성분들의 유전율을 계산하였다. 결과: 이로부터 다음과 같은 결과를 얻었다. 1. 전후방적 변수에서 골격성 I급 군은 대부분의 변수가, 골격성 II급 군에서는 SNB, facial angle이 유전율이 높은 것으로 나타났다. 2. 수직적 변수에서 골격성 I급 군은 Frankfort Horizontal plane-Palatal Plane angle, Palatal Plane angle-Mandibular Plane angle (PP-MP)에서, 골격성 II급 군은 PP-MP, 전안면 및 후안면 고경에서 유전율이 높은 것으로 나타났다. 3. 치열 변수는 골격성 I급 군에서만 높은 유전율을 보이는 계측치가 확인되었다. 4. 하악골 변수에서는 골격성 I급 군은 Condylion-Gnathion, Articulare-Gonion 길이의 유전율이 높았고, 골격성 II급 군에서는 두개저 길이를 나타내는 계측치(Sella-Nasion, Sella-Articulare, Articulare-Nasion)의 유전율이 높은 것으로 나타났다. 5. 주성분분석에서 골격성 I급 군에서는 8개, 골격성 II급 군에서는 7개의 주성분들을 추출하였고, 이 주성분들이 골격성 I급 군 특성의 88.3%, 골격성 II급 군 특성의 91.0%를 설명하는 것으로 나타났다. 결론: 골격성 I급 군과 골격성 II급 군에서 두개안면 골격 및 치열의 유전율이 서로 다르게 나타났으므로, 교정 진단과 치료 계획 수립 시 수평적 골격 양상을 고려하여 성장을 평가하고 예측하는 것이 필요하다.I. Introduction 1 II. Review of Literature 3 III. Materials and Methods 11 IV. Results 14 V. Discussion 16 VI. Conclusion 19 VII. References 20박

A morphometric approach to facial growth prediction

BACKGROUND: Orthodontists rely heavily on cephalometric analysis to assess growth potential and direction. Geometric morphometrics examines shape and can help the clinician reach more accurate diagnoses and predict future growth. PURPOSE: The aims of this study are: 1) Determine principle components describing craniofacial shape changes; 2) Assess shape changes in growing subjects; 3) Develop a model for craniofacial growth prediction using geometric morphometrics. RESEARCH DESIGN: The Cranial base, maxilla and mandible were digitized on 330 lateral cephalograms from ages 6-16 (n=33). Generalized Procrustes analysis was performed on the longitudinal data sample. Principle Component, Discriminant Function and Two-Block Partial Least Squares analysis were assessed against changes in individual structures to determine if changes in the maxillary, mandibular or cranial base are related to changes in shape of the overall craniofacial form. RESULTS: PCA shows that the first six principle components account for 67.7 – 77.0% of the observed shape variance in each region and 56.0% of the whole form. Multivariate regression analysis predicts the shape of the entire craniofacial complex at 16 years old based on the shape observed at 6 years old with 94% certainty. An intraclass correlation coefficient of 0.98 confirms reliability. CONCLUSION: Morphometric analyses indicate that changes in maxillofacial morphology during skeletal maturation are linear. The shape of the craniofacial complex does not change significantly and growth pattern is maintained. Our model can predict the craniofacial shape at 16 years of age based on the shape observed at 6 years of age

Spatially Dense 3D Facial Heritability and Modules of Co-heritability in a Father-Offspring Design

Introduction: The human face is a complex trait displaying a strong genetic component as illustrated by various studies on facial heritability. Most of these start from sparse descriptions of facial shape using a limited set of landmarks. Subsequently, facial features are preselected as univariate measurements or principal components and the heritability is estimated for each of these features separately. However, none of these studies investigated multivariate facial features, nor the co-heritability between different facial features. Here we report a spatially dense multivariate analysis of facial heritability and co-heritability starting from data from fathers and their children available within ALSPAC. Additionally, we provide an elaborate overview of related craniofacial heritability studies.Methods: In total, 3D facial images of 762 father-offspring pairs were retained after quality control. An anthropometric mask was applied to these images to establish spatially dense quasi-landmark configurations. Partial least squares regression was performed and the (co-)heritability for all quasi-landmarks (∼7160) was computed as twice the regression coefficient. Subsequently, these were used as input to a hierarchical facial segmentation, resulting in the definition of facial modules that are internally integrated through the biological mechanisms of inheritance. Finally, multivariate heritability estimates were obtained for each of the resulting modules.Results: Nearly all modular estimates reached statistical significance under 1,000,000 permutations and after multiple testing correction (p ≤ 1.3889 × 10-3), displaying low to high heritability scores. Particular facial areas showing the greatest heritability were similar for both sons and daughters. However, higher estimates were obtained in the former. These areas included the global face, upper facial part (encompassing the nasion, zygomas and forehead) and nose, with values reaching 82% in boys and 72% in girls. The lower parts of the face only showed low to moderate levels of heritability.Conclusion: In this work, we refrain from reducing facial variation to a series of individual measurements and analyze the heritability and co-heritability from spatially dense landmark configurations at multiple levels of organization. Finally, a multivariate estimation of heritability for global-to-local facial segments is reported. Knowledge of the genetic determination of facial shape is useful in the identification of genetic variants that underlie normal-range facial variation

The normal dimensions of the sella turcica in Jordanians: a study on lateral cephalograms

Background: The sella turcica is an important anatomic and radiologic entity. The dimensions of the sella turcica vary greatly in normal individuals and are influenced by genetic and local factors. The main objective of this study is to build up a normative database of the dimensions of the sella turcica in the Jordanian population. Materials and methods: For this purpose 509 computed cephalograms of 252 male and 257 female healthy Jordanians aged 10–40 years were collected and divided into two adolescent and adult age-groups for both genders. Viewbox 3 software was used to determine linear dimensions and area of the sella turcica. Results: Our results showed that the overall values for width, length, height, area, and aperture (interclinoid distance) were 8.72, 7.68, 6.25, 40.80, 3.92, and 8.67, 7.42, 6.38, 41.26, 3.68 mm (mm2) for males and females, respectively. Significant differences were found between adult male group on one hand and adolescent female group and adult female group on the other hand. Between age categories and within male and female groups, sella parameters were significantly different between adolescent and adult age-groups. Conclusions: Our data clearly confirm the classical notion of general trend of increase in parameters with age, irrespective of gender, with the area scoring the highest increase, and the height in females and length in males contributing most obviously to this trend. The aperture appears to decrease in females while it increases in males as adulthood is reached. This seems to reflect differential growth of the pituitary gland under neurohormonal effects

Heritability of nasal characteristics using lateral cephalograms

BACKGROUND: Growth of the cranial base and its structures are of particular interest to the orthodontic community. The midface and nasal bones have a significant influence on facial esthetics and thus pattern recognition of facial growth from parental data can influence orthodontic treatment plans. We aimed to determine if there is a similarity in midface and nasal bone and soft tissue growth between a child and either parent. MATERIALS AND METHODS: This cross-sectional study was comprised of forty-seven western European families from the Forsyth/Moorrees Twin Study. The lateral cephalograms of each parent and post pubertal child, who were at least 2 years past peak growth (age ≥ 16 yrs for females and ≥ 17 yrs for males) were evaluated on fourteen cephalometric variables. The radiographs were digitized and analyzed using the Mimics™ software program (Materialise, Leuven, Belgium) by a single investigator. A linear regression analysis was used to correlate linear and angular measurements to one another. An ANOVA with multiple comparisons (TUKEY) was performed to test for the differences between family members controlling for the effect of the individual family (as each family has a trend within itself). Age and gender interactions were tested for in the models. Statistical significance was set at p < 0.05. RESULTS: Twenty-five male and twenty-two female children and their parents were studied. When comparing the fourteen parameters between the mean of the child and both parents, a significant difference (p < 0.05) was found between the child and the father but not the mother in six measurements. These included the ratio of nasal height to total face height, angle of nasal bone to SN, distance from rhinion to pronasale (mm), distance from ANS to pronasale (mm), projection of nose (mm) and nasal length (mm). A significant difference was also found between the child and the mother, but not the father for rhinion to ANS (mm). A significant difference was found between the child and both parents for nasal height (mm). When controlling for family and isolating the gender of the child, males and females were not significantly different from their fathers for ratio of nasal height to total face height. For angle of nasal bone (S-N-Rh) and nasal length (N’-vertical line from Pro), females but not males were significantly different from the father. Both girls and boys were still significantly different from the father in the rhinion to pronasale and ANS to pronasale distances, projection of nose and nasal heights. Only males showed a significant difference from the mother for rhinion to ANS and nasal height when isolated for by gender. CONCLUSION: Statistically significant differences were found between the child and father and not the mother for six out of our fourteen measurements of interest. Two measurements of interest showed a difference between the child and the mother and not the father and one showed a significant difference from both parents. From this study we conclude that children tend to be morphologically less similar to their fathers when comparing midface and nasal soft and hard tissue parameters

Heritability of facial morphology

Facial recognition methodologies, widely used today in everything from automatic passport controls at airports to unlocking devices on mobile phones, has developed greatly in recent years. The methodologies vary from feature based landmark comparisons in 2D and 3D, utilising Principal Component Analysis (PCA) to surface-based Iterative Closest Point Algorithm (ICP) analysis and a wide variety of techniques in between. The aim of all facial recognition software (FCS) is to find or match a target face with a reference face of a known individual from an existing database. FCS, however, faces many challenges including temporal variations due to development/ageing and variations in facial expression. To determine any quantifiable heritability of facial morphology using this resource, one has to look for faces with enough demonstrable similarities to predict a possible genetic link, instead of the ordinary matching of the same individual’s face in different instances. With the exception of identical twins, this means the introduction of many more variables into the equation of how to relate faces to each other. Variation due to both developmental and degenerative aging becomes a much greater issue than in previous matching situations, especially when comparing parents with children. Additionally, sexual dimorphism is encountered with cross gender relationships, for example, between mothers and sons. Non-inherited variables are also encountered such as BMI, facial disfigurement and the effects of dental work and tooth loss. For this study a Trimmed Iterative Closest Point Algorithm (TrICP) was applied to three-dimensional surfaces scans, created using a white light scanner and Flexscan 3D, of the faces of 41 families consisting of 139 individuals. The TrICP algorithm produced 7176 Mesh-to-mesh Values (MMV) for each of seven sections of the face (Whole face, Eyes, Nose, Mouth, Eyes-Nose, Eyes-Nose-Mouth, and Eyes-Nose- Mouth-Chin). Receiver Operated Characteristic (ROC) analysis was then conducted for each of the seven sections of the face within 11 predetermined categories of relationship, in order to assess the utility of the method for predicting familial relationships (sensitivity/specificity). Additionally, the MMVs of three single features, (eyes, nose and mouth) were combined to form four combination areas which were analysed within the same 11 relationship categories. Overall the relationship between sisters showed the most similarity across all areas of the face with the clear exception of the mouth. Where female to female comparison was conducted the mouth consistently negatively affected the results. The father-daughter relationship showed the least similarity overall and was only significant for three of the 11 portions of the face. In general, the combination of three single features achieved greater accuracy as shown by Areas Under the Curve (AUC) than all other portions of the face and single features were less predictive than the face as a whole

Craniofacial and dental anomalies in Van der Woude and Blepharocheilodontic syndromes

Background and objectives: Cleft lip and/or palate (CL/P) is the most common orofacial birth defect, which may either be associated with other abnormalities or occur as an isolated condition. The most common syndromic form of orofacial clefting is the Van der Woude Syndrome (VWS), Blepharocheilodontic (BCD) syndrome is a rare condition characterised by eye, lip and dental developmental orofacial clefting abnormalities. The aim of this thesis was to analyse BCD syndrome phenotypes and the associated dental and craniofacial anomalies and compare it with non-syndromic bilateral cleft lip and palate (NSBCLP) and non-cleft) (study I), the prevalence, pattern and severity of taurodontism (study II), as well as the dental maturity (DM) and anomalies in individuals with VWS exhibiting cleft palate, were analyzed and compared with non-syndromic cleft palate (NSCP) and non-cleft controls (study III). Materials and methods: In study I, cephalometric radiographs of BCD syndrome patients, 20 NSBCLP and 20 non-cleft, were analysed. The clinical records, photographs, dental study casts and dental radiographs were also assessed to determine the tooth agenesis extent and pattern, dental morphology and malocclusion. For study II, one hundred and seventy-eight dental panoramic tomographs (DPTs) consisting of 42 VWS patients, 42 NSCP patients and 94 normative non-cleft children were assessed, and their first permanent molars evaluated. Measurement 3 of the taurodontism index. Prevalence, pattern, and severity were compared between groups. For study III, 204 dental panoramic tomographs (DPTs) consisted of 51 VWS patients, 51 NSCP patients and 102 normative non-cleft children were collected. Dental stages were assessed by Demirjian’s method, with the Finnish dental maturity reference values. Dental anomalies included tooth agenesis and taurodontism. Results: The results of study I revealed that BCD syndrome patients had a maxillary–mandibular sagittal discrepancy (very severe skeletal III malocclusion) and decreased anterior lower face height compared to NSBCLP and non-cleft controls (P = 0.001, P = 0.027). All patients had oligodontia (mean number of missing permanent teeth 13.7). All patients exhibited missing upper central and lateral incisors, upper canine and premolar teeth. In study II, the prevalence of taurodontic molars in children with VWS was higher than in the other groups (59.5% compared to 45.2% in the NSCP group, and 26.6% in non-cleft controls). The prevalence and severity of taurodontism in VWS and NSCP were significantly higher than in non-cleft children in all first permanent molars, while the difference between VWS and NSCP groups was not significant. Children in VWS group were approximately twice more likely to have taurodontism compared to NSCP group. Hypotaurodontism was the most frequent type in taurodontic molars. In study III, the differences between dental age (DA) and chronological age (CA) of VWS group and NSCP group were significantly lower than the difference in the non-cleft group (P= 0.002). There was no significant difference between VWS and NSCP groups (P= 0.817). Hypodontia prevalence in the non-cleft group (5.88 %) was significantly lower than both VWS group (37.25 %) (P= 0.0001) and NSCP group (19.6 %) (P= 0.035). Conclusions: The craniofacial skeletal defects in the BCD syndrome group were more severe than in patients with NSBCLP. The pattern of tooth agenesis is unusual as it included teeth that are normally highly resistant to agenesis. In VWS and NSCP we observed a high prevalence of taurodontism. Most taurodontic molars are hypotaurodontic. Dental maturity was delayed in both the VWS and NSCP groups compared to the non-cleft control. Hypodontia prevalence was significantly high in both VWS and NSCP groups compared to the non-cleft control. This thesis will provide an insight into these diseases and help clinicians develop a proper guideline for treatment protocol.Tiivistelmä ei ole saatavilla