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

Paternoster, Lavinia, Zhurov, Alexei I., Toma, Arshed M., Kemp, John P., St. Pourcain, Beate, Timpson, Nicholas J., McMahon, George, McArdle, Wendy, Ring, Susan M., Smith, George Davey, Richmond, Stephen and Evans, David M. (2012) Genome-wide association study of three-dimensional facial morphology identifies a variant in PAX3 associated with nasion position. American Journal of Human Genetics, 90 3: 478-485. doi:10.1016/j.ajhg.2011.12.021


Author Paternoster, Lavinia
Zhurov, Alexei I.
Toma, Arshed M.
Kemp, John P.
St. Pourcain, Beate
Timpson, Nicholas J.
McMahon, George
McArdle, Wendy
Ring, Susan M.
Smith, George Davey
Richmond, Stephen
Evans, David M.
Title Genome-wide association study of three-dimensional facial morphology identifies a variant in PAX3 associated with nasion position
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2012-03-09
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2011.12.021
Open Access Status DOI
Volume 90
Issue 3
Start page 478
End page 485
Total pages 8
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Subject 1311 Genetics
2716 Genetics (clinical)
Formatted abstract
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. 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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