The outermost layer of the brain is called the cerebral cortex; it's a relatively thin sheet of gray matter that receives sensory input from the body and is critical for a variety of functions including language, memory, emotion, judgment, and creativity. It has also been associated with psychiatric disorders like schizophrenia and autism, and neurodegenerative diseases including dementia, Huntington's, and Parkinson's disease.
Different parts of the body take on their specialized functions by expressing different genes, so only certain genes are expressed in the cerebral cortex. Humans carry mostly the same genes in their genomes, but individual variations arise in biology part due to small changes in the sequences of those genes.
Scientists have now taken a close look at the impact of small variations in genes that are expressed in the cerebral cortex. Using DNA and MRI scans obtained from over 50,000 individuals, they found 306 genetic variants that are thought to impact the structure of this folded brain layer. These variants may, therefore, play critical roles in various neurological and psychiatric conditions. This data will also help scientists learn more about the function of the genes carrying the variants. The findings have been reported in Science.
"This study was only possible due to a huge scientific collaboration of more than 60 sites involved in MRI scanning and genotyping participants," said the senior study author Jason Stein, Ph.D., assistant professor in the Department of Genetics at the University of North Carolina School of Medicine. "This study is the crown jewel of the ENIGMA Consortium, so far."
The international network known as the ENIGMA Consortium was co-founded ten years ago by Stein and co-senior study authors Sarah Medland, Ph.D., senior research fellow at the QIMR Berghofer Medical Research Institute in Australia; and Paul Thompson, Ph.D., associate director of the Mark and Mary Stevens Neuroimaging and Informatics Institute at the University of Southern California.
The effort has yielded a variety of new insights into how genetic variants impact the cortex. Some variants were linked to folding or surface area in the cortex, and were related to fetal cortex development. Others were connected to cortical thickness and were associated with gene expression in the adult cortex. There was a genetic tendency toward a lower cortex surface area in people who were at risk for insomnia or depression, while those at risk for Parkinson's disease were more likely to have a higher cortex surface area.
"Most of our previous understanding of genes affecting the brain are from model systems, like mice," Stein said. "With mice, we can find genes, knock out genes, or overexpress genes to see how they influence the structure or function of the brain. But there are a couple of problems with this."
Clearly, a mouse and a human are not the same, and the model is not sufficient to answer some questions about human biology.
"The genetic basis for a mouse is very different than the genetic basis for humans," Stein said, "especially in in the noncoding regions of the genome."