Team Identifies New Genes Responsible for Facial Features

Scientists from KU Leuven and the Universities of Pittsburgh, Stanford, and Penn State say they have identified fifteen genes that determine our facial features. Doctors could use DNA for skull and facial reconstructive surgery, forensic examiners could sketch a perpetrator’s face on the basis of DNA retrieved from a crime scene, and historians would be able to reconstruct facial features using DNA from the past.

The study (“Genome-Wide Mapping of Global-to-Local Genetic Effects on Human Facial Shape”) appears in Nature Genetics.

“Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined,” write the investigators.

“All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.”

“We’re basically looking for needles in a haystack,” says Seth Weinberg, Ph.D., of the departments of oral biology and anthropology at the University of Pittsburgh. “In the past, scientists selected specific features, including the distance between the eyes or the width of the mouth. They would then look for a connection between this feature and many genes. This has already led to the identification of a number of genes but, of course, the results are limited because only a small set of features are selected and tested.”

In the current study the team adopted a different approach.

“Our search doesn’t focus on specific traits,” lead author Peter Claes, Ph.D., KU Leuven, explains. “My colleagues from Pittsburgh and Penn State each provided a database with 3D images of faces and the corresponding DNA of these people. Each face was automatically subdivided into smaller modules. Next, we examined whether any locations in the DNA matched these modules. This modular division technique made it possible for the first time to check for an unprecedented number of facial features.”

The scientists were able to identify fifteen locations in our DNA. The Stanford team found out that genomic loci linked to these modular facial features are active when our face develops in the womb.

“Furthermore, we also discovered that different genetic variants identified in the study are associated with regions of the genome that influence when, where and how much genes are expressed,” adds Joanna Wysocka, Ph.D., at Stanford University School of Medicine.

Seven of the fifteen identified genes are linked to the nose, and that’s good news, according to Dr. Claes. “A skull doesn’t contain any traces of the nose, which only consists of soft tissue and cartilage. Therefore, when forensic scientists want to reconstruct a face on the basis of a skull, the nose is the main obstacle. If the skull also yields DNA, it would become much easier in the future to determine the shape of the nose.”

The four universities are continuing their research using larger databases.

“We won’t be able to predict a correct and complete face on the basis of DNA tomorrow. We’re not even close to knowing all the genes that give shape to our face. Furthermore, our age, environment, and lifestyle have an impact on what our face looks like as well,” points out Mark Shriver, Ph.D., of the department of anthropology at Penn State.