Genes responsible for growth of brain cortex discovered

Genes that control the shape and growth of the human cerebral cortex have been discovered by scientists.

The cerebral cortex controls many processes that distinguish humans from animals and are integral to our daily life, such as language and attention. While specific genetic determinants of the shape and size of the cortex have been difficult to establish in humans, new research from a group at the University of California, San Diego has identified a cohort of genes that control these attributes.

'The complexity of the human brain has equally eluded and fascinated scientists for centuries' said Dr Carolina Makowski, first author on the paper published in Science. 'A large part of how our brain is shaped boils down to what is entwined in our DNA.'

The cerebral cortex has a complex anatomy, with different regions being specialised for controlling specific mental processes. Previous studies have linked genes to the growth of cortical regions based on anatomical definitions. To make their research more genetically guided, Dr Makowski and her colleagues instead defined the different cortical regions in an atlas based on the genes that are known to guide the development of the cortex in the fetus.

Comparing the approach to planning a car trip, Dr Makowski noted 'you would likely turn to a road map or GPS to navigate your way around, and you would be less interested in consulting other maps based on topography'.

'Similarly, how we define brain regions should depend on the research question at hand. With this approach of using genetically defined atlases, we were able to uncover the largest number of genetic variants to date associated with the size and thickness of the cortex.'

The brain atlases were used in a genome-wide association study (GWAS) of 12 cortical regions for thickness and surface area, using genomic and brain scan data from 32,488 people stored in the UK Biobank. The analysis identified 440 genes that control the size and shape of these regions — the largest number yet.

Because previous studies based on an anatomically defined atlas had used adults only, the group then looked at data from 9136 children participating in the Adolescent Brain Cognitive Development study. They found that their observations from adults were statistically correlated with the childhood data, suggesting that – to some extent – these observations can also be generalised to younger brains that have not finished developing.

'Intriguingly, many of the genes that these loci map to are also associated with neurodevelopmental disorders, such as autism, epilepsy and intellectual disability, and dementia,' said Dr Chi-Hua Chen, the senior author of the study. 'The loci we discovered can be used by researchers for further mechanistic studies of how genes impact the brain and diseases.'