Genetics of human face begin to reveal underlying profile

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The researchers added 7000 data points on 3D images of the face. The red and blu
The researchers added 7000 data points on 3D images of the face. The red and blue colours respectively indicate outward and inward displacement of the facial shape, associated with two example genetic locations. One (left) specifically affects the shape of the forehead, the other (right) affects the shape of the centre of our face.

In an international study led by KU Leuven and Pennsylvania State University, researchers have identified 203 genes that play a role in the shape of our face. Their study was published.

The genetics behind the shape of the human face are difficult to decipher. In 2018, KU Leuven Professor Peter Claes and international colleagues, from Penn State, the University of Pittsburgh and Stanford University School of Medicine, already identified 15 genes that can be connected with specific areas of the face. Building on this work, with additional colleagues from Indiana University - Purdue University Indianapolis and Cardiff University, they now identified a total of 203 genetic locations involved in craniofacial development, 53 of which have never been reported before.

They not only can see the signals of normal facial features in the genome, but also hope their work can shed light on craniofacial malformations such as cleft lip and palate. Understanding the genetics of normal facial structure can also help us understand the evolution of the face. Another possible use is in forensics, though there is a long way to go until DNA facial reconstructions can become a reality.

"The face tells the outside world about your identity, who you are related to, where your ancestors come from and even your health," says Julie White of Penn State, one of the joint first authors of the study. "But we only know a fraction of how faces are formed," adds Dr. Karlijne Indencleef of KU Leuven, the other first author of the study. "The facial structure comes together in early development, and if it doesn’t go right, you can get a cleft palate or other problem. We don’t fully know what controls those processes," she added.

In many cases of facial dysmorphology, there are limited numbers of subjects, making it difficult to scour large data sets looking for errant genes. However, the researchers believe that the genetic location for lip formation in the larger, non-clinical population might also contribute to malformations of the lip.

Gridded mask

The researchers used two data sets, one from the U.K. (the Avon Longitudinal Study of Parents and Children), containing 3,566 individuals and one from the U.S. containing 4,680 individuals. The data sets consisted of both the full DNA and a highly detailed 3D facial photograph of the subjects. The researchers placed over 7,000 point locations on the images using a gridded mask that was digitally stretched and pulled to conform to the facial contours of each individual.

Next, they divided the face into 63 segments using data-driven relationships. This allowed the researchers to look at variation in small subsets of the entire face.

To give more power to the study, the researchers considered the U.S. data set and the U.K. data set separately, alternating between the two to find and then replicate genetic sites associated with facial features. Eventually, looking at only genetic locations that had similar associations in both datasets, they identified 203 genomic regions that are significant for facial structure. Of these, 89 had already been found in other studies, either using the same data or with independent data. Of the remaining 144 locations, 61 were already implicated as the source of facial malformations in humans or mice, and 53 locations were completely new to this study.

"The additional epigenetic analyses showed that the genetic regions we found get expressed in cells relevant for craniofacial development, which is an important strong and first validation of the genetic loci identified", said Indencleef. "However, we have merely tagged the locations. It is of strong interest for wet labs to validate and further investigate their exact functions"

"Collaborations in jointly analyzing multiple datasets in combinations with better analysis techniques are key to push this research," said Professor Peter Claes, Professor of engineering science (ESAT-PSI) and human genetics at KU Leuven, who pioneered the 3D analysis method.

Shared genetics

"If you compare what we found with previous literature, you see an overlap with our genes and genes that had previously been implicated in non-facial things such as limb development and organ and skeletal abnormalities," said White. "There are shared genetics. Things that are related to the face and related to another part of the body."

Some facial deformities are associated with other physical problems, so finding shared genetics was not surprising, according to the researchers. However, understanding shared genetics will help to understand the formation of facial malformation, and potentially identify the factors specific to these deformities. Many of the genes identified begin working in the early stages of embryonic development, a stage that is influential to many different aspects of our physical presentation as adults. However, according to the researchers, even with all of these genetic loci combined they remain falsely predictive of one single physical aspect.