Genetic Analysis of Normal Human Facial Variation

The purpose of this project is to identify genes associated with normal human quantitative facial variation. The motivation for this project stems from the fact that very little is known about how variation in specific genes relates to the diversity of facial forms commonly observed in humans. Viable candidates for these morphogenes originate from a number of sources: tissue expression studies, animal models with targeted or spontaneous mutations, and genetic syndromes with craniofacial manifestations. Importantly, understanding the genetic basis for normal facial variation also has important implications for health-related research. For example, this work has the potential to shed light on the factors influencing liability to common craniofacial anomalies such as orofacial clefts. There is now ample evidence that certain facial features (e.g., increased midfacial retrusion) characterize individuals genetically at-risk for orofacial clefts (e.g., biological relatives of affected cases). While these predisposing facial features are statistically over-represented in at-risk groups, they are also common in the general population. Since many of the current candidate genes for clefting are thought to play a critical role in facial morphogenesis, variation in these genes may also underlie normal variation in these facial features. These candidate genes, however, probably represent only a small fraction of the total number of loci influencing normal human facial variation. Phenotypes for this project were obtained from over 3000 healthy Caucasian subjects recruited through three separate studies. The majority of the subjects were recruited as part of the 3D Facial Norms Project, which is described in extensive detail here: (https://www.facebase.org/facial_norms/notes). The provided dbGaP phenotypes include a series of anthropometric craniofacial measurements (linear distances) primarily derived from 3D photographic facial surface scans (see previous hyperlink). The specific genotyping requested is described elsewhere in this document. Our analysis team is pursuing a variety of different analytic approaches to derive genetically informative phenotypes, including various shape-based morphometric methods. For those interested in pursuing more advanced phenotypic approaches, the original 3D surface scans and additional phenotypic traits are available to researchers through the FaceBase Consortium. This dataset has the potential to facilitate the discovery of new genetic loci with an important role in both normal and abnormal facial development. It may also serve as a dataset to test hypotheses regarding specific SNP associations (e.g. as a replication dataset) or as part of a larger meta-analysis.]]>
3D Facial Norms Dataset and POFC Control Dataset Inclusion Criteria: Self-identified European Caucasian Ancestry Age 3-40 years (extended to 60 years for POFC) Exclusion Criteria: A personal history of facial trauma or disfigurement A personal history of facial reconstructive or plastic surgery A personal history of orthognathic/jaw surgery or jaw advancement A personal history of any facial prosthetics or implants A personal history of any palsy, stroke or neurological condition affecting the face A personal or family history of any facial anomaly or birth defect A personal or family history of any syndrome or congenital condition with a facial manifestation The presence of any non-removable facial piercings other than small studs The presence of conspicuous facial hair Spritz FaceBase Dataset Inclusion Criteria: Self-identified European Caucasian Ancestry Exclusion Criteria: A personal history of facial trauma or disfigurement A personal history of any facial surgery A personal or family history of any facial anomaly or birth defect A personal or family history of any syndrome or congenital condition with a facial manifestation ]]>
The data for this project were collected through a collaborative effort involving several independent studies. The bulk of the data was collected though the 3D Facial Norms project (U01DE020078: PIs Seth M. Weinberg and Mary L. Marazita), which was part of the FaceBase Consortium. The subjects for this project were collected at four US cities: Pittsburgh, Seattle, Houston and Iowa City. 3D facial images were collected using the 3dMDface system. The strategy for recruitment involved a combination of targeted advertisement, peer referral, leveraging existing research registries, and participation at public venues. More details about this study can be found here: https://www.facebase.org/facial_norms/notes Just under 800 subjects were collected as part of a separate FaceBase project under the direction of Richard Spritz (U01DE020054: PI Richard A. Spritz). The subjects for this project were collected at either Denver or San Francisco. 3D facial images were collected using the Creaform Gemini camera system. Additional subjects were recruited as controls during a study of the genetics of orofacial clefting (Pittsburgh OroFacial Cleft or POFC; Mary L. Marazita, PI; R01DE016148). These subjects were collected at several us sites, including Pittsburgh, St. Louis and Iowa City. 3D facial images were collected using the 3dMDface system. The phenotypic measurements included in this dataset are standard anthropometric facial measurements (inter-landmark distances). The details of these measurements and the facial landmarks that were used to calculate them can be found here: https://www.facebase.org/facial_norms/notes]]>