Genetic differences influence the physical properties of the brain’s cerebral cortex and likely play a key role in cognition and risk of neurological conditions, including Parkinson’s disease, a new study has found.
Titled “The genetic architecture of the human cerebral cortex,” the study was published in the journal Science.
The cerebral cortex, the highly-folded outer layer of the brain, is a region crucial for processing information, memory, thinking, and attention. There are differences between individuals in the physical properties of the cerebral cortex, such as its thickness and surface area (essentially, how densely folded the tissue is). Some of these differences have previously been linked to conditions such as attention deficit hyperactivity disorder (ADHD) and schizophrenia, as well as to cognition in general.
Genetics play an important role in guiding the development of the brain. But, to date, most studies on the genetics underpinning brain development have been done in mice, making it difficult to draw conclusions about human biology.
“The genetic basis for a mouse is very different than the genetic basis for humans,” Jason Stein, PhD, professor at the University of North Carolina School of Medicine and co-author of the new study, said in a press release.
In the study, researchers collected magnetic resonance imaging (MRI) scans, as well as genetic data, of 51,665 people.
“This study was only possible due to a huge scientific collaboration of more than 60 sites involved in MRI scanning and genotyping participants,” Stein said.
By combining the MRI and genotype data, the researchers identified 306 regions in the genome where variations in the DNA code were significantly associated with differences in the thickness and/or surface area of the cerebral cortex. Of these, 299 regions had data available for replication and 199 regions remained significant after several statistical analyses.
Collectively, genetic variations accounted for 34% of the variation in surface area and 26% of the variation in thickness (the rest of the variation would be determined by other factors, such as the environment in which a person lives).
Subsequent analysis of the regions in question revealed that genes associated with surface area were generally active early on in fetal development. In contrast, genes involved in regulating thickness were more active during adulthood.
Interestingly, many of these variations were in parts of the genome that don’t code for proteins (non-coding regions). While historical biological understanding was that genes encode proteins, which then carry out functions, this study adds to an accumulating wealth of evidence showing that non-coding parts of the genome also have important functions.
The researchers noted significant associations between cerebral cortex surface area and both general cognitive functioning and educational attainment. In other words, individuals with higher cortex surface areas were more likely to have greater cognition and to have had more education. The statistical analysis suggested that this was a bidirectional causation relationship. In other words, there was evidence to suggest that higher brain surface area caused people to have better cognition, and also that having higher cognition caused brain surface area to increase.
Significant associations were found between high cortex surface area and genetic risk for Parkinson’s disease, but there was no evidence of a cause-and-effect relationship.
Overall, the study provides new insight into how genetic variations help to control the development of the brain.
“This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning,” the researchers said.
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