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Novel genetic loci affecting facial shape variation in humans.

ABSTRACT: The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10-8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10-3). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

SUBMITTER: Xiong Z

PROVIDER: S-EPMC6905649 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Novel genetic loci affecting facial shape variation in humans.

Xiong Ziyi Z Dankova Gabriela G Howe Laurence J LJ Lee Myoung Keun MK Hysi Pirro G PG de Jong Markus A MA Zhu Gu G Adhikari Kaustubh K Li Dan D Li Yi Y Pan Bo B Feingold Eleanor E Marazita Mary L ML Shaffer John R JR McAloney Kerrie K Xu Shu-Hua SH Jin Li L Wang Sijia S de Vrij Femke Ms FM Lendemeijer Bas B Richmond Stephen S Zhurov Alexei A Lewis Sarah S Sharp Gemma C GC Paternoster Lavinia L Thompson Holly H Gonzalez-Jose Rolando R Bortolini Maria Catira MC Canizales-Quinteros Samuel S Gallo Carla C Poletti Giovanni G Bedoya Gabriel G Rothhammer Francisco F Uitterlinden André G AG Ikram M Arfan MA Wolvius Eppo E Kushner Steven A SA Nijsten Tamar Ec TE Palstra Robert-Jan Ts RT Boehringer Stefan S Medland Sarah E SE Tang Kun K Ruiz-Linares Andres A Martin Nicholas G NG Spector Timothy D TD Stergiakouli Evie E Weinberg Seth M SM Liu Fan F Kayser Manfred M

eLife 20191126

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10<sup>-8</sup>), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 791 ...[more]

PMID: 31763980

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Project description:IntroductionThe regular collection of 3-dimensional (3D) imaging data is critical to the development and implementation of accurate predictive models of facial skeletal growth. However, repeated exposure to x-ray-based modalities such as cone-beam computed tomography has unknown risks that outweigh many potential benefits, especially in pediatric patients. One solution is to make inferences about the facial skeleton from external 3D surface morphology captured using safe nonionizing imaging modalities alone. However, the degree to which external 3D facial shape is an accurate proxy of skeletal morphology has not been previously quantified. As a first step in validating this approach, we tested the hypothesis that population-level variation in the 3D shape of the face and skeleton significantly covaries.MethodsWe retrospectively analyzed 3D surface and skeletal morphology from a previously collected cross-sectional cone-beam computed tomography database of nonsurgical orthodontics patients and used geometric morphometrics and multivariate statistics to test the hypothesis that shape variation in external face and internal skeleton covaries.ResultsExternal facial morphology is highly predictive of variation in internal skeletal shape ([Rv] = 0.56, P <0.0001; partial least squares [PLS] 1-13 = 98.7% covariance, P <0.001) and asymmetry (Rv = 0.34, P <0.0001; PLS 1-5 = 90.2% covariance, P <0.001), whereas age-related (r(2) = 0.84, P <0.001) and size-related (r(2) = 0.67, P <0.001) shape variation was also highly correlated.ConclusionsSurface morphology is a reliable source of proxy data for the characterization of skeletal shape variation and thus is particularly valuable in research designs where reducing potential long-term risks associated with radiologic imaging methods is warranted. We propose that longitudinal surface morphology from early childhood through late adolescence can be a valuable source of data that will facilitate the development of personalized craniodental and treatment plans and reduce exposure levels to as low as reasonably achievable.

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Novel genetic loci affecting facial shape variation in humans.

Publications

Novel genetic loci affecting facial shape variation in humans.

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