Human Head Shape Diversity Uncovered; Study Reveals Genetic Basis of Conditions Affecting the Skull

Within and among human populations, the cranial vault shows considerable variation in size and shape. This space in the skull is clinically relevant, yet its genetic architecture remains poorly understood. In a new collaborative study, scientists have identified the genes that influence the shape of the human head.

What is a Cranial Vault?

The cranial vault is the space surrounding and enclosing the skull's brain. Also known as calvarium, this case is formed from several plates of bones that meet at sutural joints and display various morphologies specific to each suture.

The cranial vault develops from the membranous neurocranium. It is composed of flat bones, which include the interparietal part of the occipital bone, the squamous part of the paired temporal bones, paired parietal bones, and paired frontal bones.

In newborns, the cranial vault is imperfectly composed to allow the large human head to pass through the birth canal. The brain's size, shape, and surrounding vault remain quite plastic as the brain grows during childhood. The head shape was altered in ancient civilizations for religious or aesthetic reasons.

Genetics Behind Human Head Shape

Since the early 20th century, anthropologists have speculated and debated the genetics of human head shape. From rare human conditions and animal experiments, experts knew that genes play a significant role in cranial vault size and shape. However, very little was known about the genetic basis for typical features in the general population.

Understanding the factors that influence natural variation in the cranial vault could help gain better insights into the early development of modern humans. Prior genetic studies involved a small number of relatively simple measures that might be easy to obtain but failed to capture biologically relevant features.

Researchers at the University of Pittsburgh and KU Leuven conducted a joint multi-ancestry genome-wide association assessment on the shape of 3D cranial vaults in humans. The study "Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape" provides clues about the genetic basis of health conditions that affect the skull.

Led by oral and craniofacial sciences professor Seth Weinberg from the Pitt School of Dental Medicine, the research team used magnetic resonance (MR) scans from over 6,000 adolescents. The 3D vault surfaces they extracted were divided into incrementally smaller anatomical subparts, and the shape of these subparts was further quantified. They also analyzed over 10 million genetic variants for evidence of statistical association with measures of vault shape.

Scientists have discovered that many strong associations are near the genes that play key roles in the early development of the head and face and the regulation of bone development. For instance, variants in and near the gene RUNX2, a major contributor to skull development, were associated with multiple aspects of head shape. Although some genes had global effects on the entire vault, others showed more localized effects that only influenced a specific portion, such as the central forehead.

According to Weinberg, the findings may reveal clues about the basis of diseases that involve the cranial vault, such as craniosynostosis. Without surgery, this condition can cause permanent brain damage and even death. The researchers show that variants near three genes associated with vault shape - ZIC2, BBS9, and BMP2 - were also associated with craniosynostosis. This suggests that these genes could also play a role in the development of the disease.