Genes Shape the Brain: New Study Decodes Genetic Influences on Brain Structure

16 June 2025

A research team has identified genetic factors that influence the shape of subcortical brain regions – far beyond volume measurements. The results could open up new approaches for the early detection of neurological and mental disorders.

The large-scale study led by Forschungszentrum Jülich, Heinrich Heine University Düsseldorf, and Helmholtz Munich examined the genetic influences on the shape of certain brain regions. The researchers focused on 22 subcortical structures, including the cerebellum. For the analysis, they used data from around 20,000 healthy White-British UK Biobank participants.

More than just volume: the importance of brain shape

“Previous studies on brain morphology focused on parameters such as volume and surface area,” explains Kaustubh Patil from the Jülich Institute of Neuroscience and Medicine. “However, these parameters do not capture the complex geometric properties of brain structures.” To describe the shape in more detail, the scientists used the Laplace-Beltrami spectrum (LBS). This describes the geometric properties of a shape using a series of numbers known as eigenvalues. By doing this, the researchers obtained a “fingerprint” of the shape of each brain region.

Genetic influences on brain shape

For each of the 22 brain structures, the researchers conducted a multivariate genome-wide association study (GWAS). They used a statistical method that makes it possible to analyse several features simultaneously – in this case the first 49 eigenvalues of each structure. The aim was to identify genetic variants associated with the shape of these structures.

“In this way, we identified 80 genetic variants that are associated with the LBS – or to put it simply, with the shape of at least one of the 22 subcortical brain structures examined,” explains co-author Sabrina Primus from Helmholtz Munich. “The brain stem stood out with a high number of relevant variants – 37 in total.” Interestingly, the identified genetic variants are already known to influence the volume of certain brain regions. What the study now shows is that they also influence the complex shape of these regions.

Links to health risks

Associations between some of the identified genetic variants and high blood pressure, neurodegeneration, alcohol consumption, and mental disorders are already known thanks to previous studies. This suggests that changes in brain shape could potentially be used as early biomarkers for these conditions.

“The study expands our understanding of how genetic factors influence not only brain size but also brain shape,” says Patil. “The results suggest that the shape of brain structures could be an important indicator of susceptibility to certain health risks. In the long term, they could be used to help develop early diagnostic methods for neurodegenerative and mental disorders.”

Original publication: Beyond volume: Unraveling the genetics of human brain geometry, by Sabrina A. Primus, Felix Hoffstaedter, Federico Raimondo, Simon B. Eickhoff, Juliane Winkelmann, Konrad Oexle, Kaustubh R. Patil, Science Advances
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