Researchers at the University of Pittsburgh and the University of Leuven have discovered a group of genes that play a role in determining the shape of the human head. Their research, recently published in Nature Communications, reveals the diversity of human head shapes. In addition, they have discovered genetic factors for conditions such as cranial dysplasia, which affects skull formation.

The study involved analyzing the cranial vault, the upper part of the skull that surrounds the brain. Through analysis, 30 genetic regions related to various head shapes were discovered, 29 of which were newly discovered in this study.

"Anthropologists have speculated and debated the genetics of cranial vault shape since the early 20th century," said co-first author Seth Weinberg, Ph.D., professor of oral and craniofacial sciences and co-director of the Center for Craniofacial and Dental Genetics at the Pittsburgh School of Dentistry. "We know from certain rare human conditions and from animal experiments that this genetics "It plays an important role in the size and shape of the dome, but little is known about the genetic basis of the typical traits we see in the general population, such as what makes someone's head grow longer and narrower, and what makes someone's head grow shorter and wider."

Research significance and applications

The researchers believe that one application of better understanding the factors that drive natural variation in human head shape is to inform paleoanthropological studies, potentially revealing the early development of modern humans.

Weinberg and colleagues used magnetic resonance (MR) scans of more than 6,000 adolescents to extract a three-dimensional surface that corresponds to the skull dome. After dividing the three-dimensional cranial surface into progressively smaller anatomical subsections and quantifying the shapes of these subsections, they tested more than 10 million genetic variants for statistical evidence related to cranial shape measurements.

Weinberg added: "Previous genetic studies of the cranial vault have involved only a small number of relatively simple measurements. While such measurements are often easy to obtain, they may not capture biologically relevant characteristics. Our analysis uses an innovative approach that allows for a more comprehensive and detailed description of cranial vault shape in three dimensions. This approach improves our ability to discover genetic associations."

An important finding is that genes near many strongly associated genes play key roles in the early formation of the head and face and in the regulation of bone development. For example, variants in and near the RUNX2 gene, a major player in coordinating skull development, are linked to multiple aspects of dome shape.

Some genes, including RUNX2, have a global effect on the entire dome, while others show a more local effect, affecting only specific parts of the dome, such as the middle of the forehead.

The researchers compared 30 genomic regions associated with head shape in European, African and Native American ancestors and found that most genes in these different ancestral groups were related to head shape.

Although the study focused on healthy participants, the findings may reveal important clues involving the biological basis of cranial diseases, Weinberg said.

Implications for understanding cranial diseases

One such disorder is cranial dysplasia, which occurs when the skull bones fuse prematurely while the brain is still growing rapidly. Without neurosurgery, cranial dysplasia can lead to permanent disfigurement, brain damage, blindness, and even death. The team found that variants near three genes involved in dome shape, BMP2, BBS9 and ZIC2, were also associated with cranial dysplasia, suggesting that these genes may play a role in the development of the disease.

"This kind of research is possible because of government-funded resources," Weinberg said. "The original research that produced these MRI scans focused on understanding brain development and behavior. By creatively leveraging these resources, we have successfully advanced discoveries beyond the original scope."

Compiled source: ScitechDaily