Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances.

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of teeth' using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P < 5 × 10(-8)) for 'age at first tooth' and 11 loci for 'number of teeth'. Together, these associations explain 6.06% of the variation in 'age of first tooth' and 4.76% of the variation in 'number of teeth'. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including an SNP in the protein-coding region of BMP4 (rs17563, P = 9.080 × 10(-17)). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development.

Genome-wide association study of three-dimensional facial morphology identifies a variant in PAX3 associated with nasion position.

Craniofacial morphology is highly heritable, but little is known about which genetic variants influence normal facial variation in the general population. We aimed to identify genetic variants associated with normal facial variation in a population-based cohort of 15-year-olds from the Avon Longitudinal Study of Parents and Children. 3D high-resolution images were obtained with two laser scanners, these were merged and aligned, and 22 landmarks were identified and their x, y, and z coordinates used to generate 54 3D distances reflecting facial features. 14 principal components (PCs) were also generated from the landmark locations. We carried out genome-wide association analyses of these distances and PCs in 2,185 adolescents and attempted to replicate any significant associations in a further 1,622 participants. In the discovery analysis no associations were observed with the PCs, but we identified four associations with the distances, and one of these, the association between rs7559271 in PAX3 and the nasion to midendocanthion distance (n-men), was replicated (p = 4 × 10(-7)). In a combined analysis, each G allele of rs7559271 was associated with an increase in n-men distance of 0.39 mm (p = 4 × 10(-16)), explaining 1.3% of the variance. Independent associations were observed in both the z (nasion prominence) and y (nasion height) dimensions (p = 9 × 10(-9) and p = 9 × 10(-10), respectively), suggesting that the locus primarily influences growth in the yz plane. Rare variants in PAX3 are known to cause Waardenburg syndrome, which involves deafness, pigmentary abnormalities, and facial characteristics including a broad nasal bridge. Our findings show that common variants within this gene also influence normal craniofacial development.

Facial fluctuating asymmetry is not associated with childhood ill-health in a large British cohort study.

The idea that symmetry in facial traits is associated with attractiveness because it reliably indicates good physiological health, particularly to potential sexual partners, has generated an extensive literature on the evolution of human mate choice. However, large-scale tests of this hypothesis using direct or longitudinal assessments of physiological health are lacking. Here, we investigate relationships between facial fluctuating asymmetry (FA) and detailed individual health histories in a sample (n = 4732) derived from a large longitudinal study (Avon Longitudinal Study of Parents and Children) in South West England. Facial FA was assessed using geometric morphometric analysis of facial landmark configurations derived from three-dimensional facial scans taken at 15 years of age. Facial FA was not associated with longitudinal measures of childhood health. However, there was a very small negative association between facial FA and IQ that remained significant after correcting for a positive allometric relationship between FA and face size. Overall, this study does not support the idea that facial symmetry acts as a reliable cue to physiological health. Consequently, if preferences for facial symmetry do represent an evolved adaptation, then they probably function not to provide marginal fitness benefits by choosing between relatively healthy individuals on the basis of small differences in FA, but rather evolved to motivate avoidance of markers of substantial developmental disturbance and significant pathology.

Three-dimensional quantification of facial symmetry in adolescents using laser surface scanning.

Laser scanning is a non-invasive method for three-dimensional assessment of facial morphology and symmetry. The aim of this study was to quantify facial symmetry in healthy adolescents and explore if there is any gender difference. Facial scans of 270 subjects, 123 males and 147 females (aged 15.3 ± 0.1 years, range 14.6-15.6), were randomly selected from the Avon Longitudinal Study of Parents and Children. Facial scans were processed and analysed using in-house developed subroutines for commercial software. The surface matching between the original face and its mirror image was measured for the whole face, upper, middle, and lower facial thirds. In addition, 3 angular and 14 linear parameters were measured. The percentage of symmetry of the whole face was significantly lower in males (53.49 ± 10.73 per cent) than in females (58.50 ± 10.27 per cent; P < 0.01). There was no statistically significant difference in the amount of symmetry among facial thirds within each gender (P > 0.05). Average values of linear parameters were less than 1 mm and did not differ significantly between genders (P > 0.05). One angular parameter showed slight lip line asymmetry in both genders. Faces of male 15-year-old adolescents were less symmetric than those of females, but the difference in the amount of symmetry, albeit statistically significant, may not be clinically relevant. Upper, middle, and lower thirds of the face did not differ in the amount of three-dimensional symmetry. Angular and linear parameters of facial symmetry did not show any gender difference.

A three-dimensional analysis of the effect of atopy on face shape.

Three-dimensional (3D) imaging technology has been widely used to analyse facial morphology and has revealed an influence of some medical conditions on craniofacial growth and morphology. The aim of the study is to investigate whether craniofacial morphology is different in atopic Caucasian children compared with controls. Study design included observational longitudinal cohort study. Atopy was diagnosed via skin-prick tests performed at 7.5 years of age. The cohort was followed to 15 years of age as part of the Avon Longitudinal Study of Parents and Children (ALSPAC). A total of 734 atopic and 2829 controls were identified. 3D laser surface facial scans were obtained at 15 years of age. Twenty-one reproducible facial landmarks (x, y, z co-ordinates) were identified on each facial scan. Inter-landmark distances and average facial shells for atopic and non-atopic children were compared with explore differences in face shape between the groups. Both total anterior face height (pg-g, pg-men) and mid-face height (Is-men, sn-men, n-sn) were longer (0.6 and 0.4mm respectively) in atopic children when compared with non-atopic children. No facial differences were detected in the transverse and antero-posterior relationships. Small but statistically significant differences were detected in the total and mid-face height between atopic and non-atopic children. No differences were detected in the transverse and antero-posterior relationships.

The influence of asthma on face shape: a three-dimensional study.

Respiratory activity may have an influence on craniofacial development and interact with genetic and environmental factors. It has been suggested that certain medical conditions such as asthma have an influence on face shape. The aim of the study is to investigate whether facial shape is different in individuals diagnosed as having asthma compared with controls. Study design included observational longitudinal cohort study. Asthma was defined as reported wheezing diagnosed at age 7 years and 6 months. The cohort was followed to 15 years of age as part of the Avon Longitudinal Study of Parents and Children. A total of 418 asthmatics and 3010 controls were identified. Three-dimensional laser surface facial scans were obtained. Twenty-one reproducible facial landmarks (x, y, z co-ordinates) were identified. Average facial shells were created for asthmatic and non-asthmatic males and females to explore surface differences. The inter-ala distance was 0.4mm wider (95% CI) and mid-face height was 0.4mm (95% CI) shorter in asthmatic females when compared with non-asthmatic females. No facial differences were detected in male subjects. Small but statistically significant differences were detected in mid-face height and inter-ala width between asthmatic and non-asthmatic females. No differences were detected in males. The lack of detection of any facial differences in males may be explained by significant facial variation as a result of achieving different stages of facial growth due to pubertal changes, which may mask any underlying condition effect.

Three-dimensional longitudinal assessment of facial symmetry in adolescents.

Recent advances in laser scanning technology provide the opportunity to examine faces in three dimensions. The aim of this prospective clinical study was to explore facial symmetry in healthy growing individuals and determine whether asymmetric changes occur during adolescent growth. Non-invasive laser surface scanning was performed to capture facial images of 60 Caucasian Finnish adolescents (30 males and 30 females, mean 11.5 years). Facial symmetry was analysed on images obtained at the initial scanning (T1), 2.5 (T2), and 4.5 (T3) years thereafter. The final sample consisted of 39 adolescents (19 males and 20 females, mean 16 years). Three-dimensional images were processed and analysed using an in-house developed subroutine for commercial software. A mirror image was generated and superimposed on the original image to create a symmetric face and establish the midsagittal plane. The surface matching of the original face and the mirror face (amount of symmetry) was measured for the whole face, upper, middle, and lower thirds at tolerance level 0.5 mm and presented with colour maps. Three angular and 14 linear measurements were made based on 21 soft tissue landmarks, which have proven to be reliable. The results of the Friedman test showed that facial symmetry parameters did not significantly differ over time (P > 0.05). Mann-Whitney U-test did not reveal statistically significant differences between genders at any time point (P > 0.05). Facial growth of healthy individuals during adolescence is symmetric, although further investigation on larger randomized sample is suggested.

The assessment of facial variation in 4747 British school children.

The aim of this study is to identify key components contributing to facial variation in a large population-based sample of 15.5-year-old children (2514 females and 2233 males). The subjects were recruited from the Avon Longitudinal Study of Parents and Children. Three-dimensional facial images were obtained for each subject using two high-resolution Konica Minolta laser scanners. Twenty-one reproducible facial landmarks were identified and their coordinates were recorded. The facial images were registered using Procrustes analysis. Principal component analysis was then employed to identify independent groups of correlated coordinates. For the total data set, 14 principal components (PCs) were identified which explained 82 per cent of the total variance, with the first three components accounting for 46 per cent of the variance. Similar results were obtained for males and females separately with only subtle gender differences in some PCs. Facial features may be treated as a multidimensional statistical continuum with respect to the PCs. The first three PCs characterize the face in terms of height, width, and prominence of the nose. The derived PCs may be useful to identify and classify faces according to a scale of normality.

A population-based cross-sectional study of the association between facial morphology and cardiometabolic risk factors in adolescence.

OBJECTIVE: To determine whether facial morphology is associated with fasting insulin, glucose and lipids independent of body mass index (BMI) in adolescents. DESIGN: Population-based cross-sectional study. SETTING: Avon Longitudinal Study of Parents and Children (ALSPAC), South West of England. PARTICIPANTS: From the ALSPAC database of 4747 three-dimensional facial laser scans, collected during a follow-up clinic at the age of 15, 2348 white British adolescents (1127 males and 1221 females) were selected on the basis of complete data on cardiometabolic parameters, BMI and Tanner's pubertal stage. MAIN OUTCOME MEASURES: Fasting insulin, glucose and lipids (triglycerides, high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc)). RESULTS: On the basis of the collection of 63 x, y and z coordinates of 21 anthropometric landmarks, 14 facial principal components (PCs) were identified. These components explained 82% of the variation in facial morphology and were used as exposure variables. With adjustment for age, gender and pubertal stage, seven PCs were associated with fasting insulin, none with glucose, three with triglycerides, three with HDLc and four with LDLc. After additional adjustment for BMI, four PCs remained associated with fasting insulin, one with triglycerides and two with LDLc. None of these associations withstood adjustment for multiple comparisons. CONCLUSIONS: These initial hypotheses generating analyses provide no evidence that facial morphology is importantly related to cardiometabolic outcomes. Further examination might be warranted. Facial morphology assessment may have value in identifying other areas of disease risk.

[New perspectives on craniofacial growth]. / Nouvelles perspectives sur la croissance cranio-faciale.

There are subtle facial differences that make people unique. We can distinguish between individuals of different gender, age, ethnicity, race and face type. Traditionally, orthodontists have approached facial assessment using lateral skull and posterior/anterior radiographs which could be combined to build a three-dimensional assessment. The aim of this article is to present an outline for a new way of looking at facial growth.