The cerebral cortex is the
relatively thin, folded, outer “gray matter” layer of the brain crucial for
thinking, information processing, memory, and attention. Not much has been
revealed about the genetic underpinnings that influence the size of the
cortex’s surface area and its thickness, both of which have previously been
linked to various psychiatric traits, including schizophrenia, bipolar
disorder, depression, attention deficit hyperactivity disorder (ADHD), and
autism.
Now, for the first time, more 360
scientists from 184 different institutions — including UNC-Chapel Hill — have
contributed to a global effort to find more than 200 regions of the genome and
more than 300 specific genetic variations that affect the structure of the
cerebral cortex and likely play important roles in psychiatric and neurological
conditions.
The study,
published in Science, was led by co-senior
authors Jason Stein, PhD, assistant professor in the Department of Genetics at
the UNC School of Medicine; Sarah Medland, PhD, senior research fellow at the
QIMR Berghofer Medical Research Institute in Australia; and Paul Thompson, PhD,
associate director of the Mark and Mary Stevens Neuroimaging and Informatics
Institute at the University of Southern California. Ten years ago, these
scientists cofounded the ENIGMA Consortium, an international research network
that has brought together hundreds of imaging genomics researchers to
understand brain structure, function, and disease based on brain imaging and
genetic data.
“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. “This study is the crown jewel of the
ENIGMA Consortium, so far.”
The researchers studied MRI scans
and DNA from more than 50,000 people to identify 306 genetic variants that
influence brain structure in order to shed light on how genetics contribute to
differences in the cerebral cortex of individuals. Genetic variants or
variations are simply the slight genetic differences that make us unique.
Generally speaking, some variants contribute to differences such as hair color
or blood type. Some are involved in diseases. Most of the millions of genetic
variants, though, have no known significance. This is why pinpointing genetic
variants associated with cortex size and structure is a big deal. Stein and
colleagues consider their new genetic roadmap of the brain a sort of “Rosetta
stone” that will help translate how some genes impact physical brain structure
and neurological consequences for individuals.
Among the
findings of the research published in Science:
·
Some genetic variants are associated with cortical
folding, measured as surface area, while other genetic variants are associated
with the thickness of the cortex.
·
Genes that determine surface area are related to very
early development in the fetal cortex, while thickness appears to be driven by
genes active in the adult cortex.
·
People at genetic risk for depression or insomnia are
genetically inclined toward having lower surface area, while people with a
genetic risk for Parkinson’s disease tend to have higher surface area.
·
The vast scale of the project allowed the discovery of
specific genes that drive brain development and aging in people worldwide.
“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 over express genes to see
how they influence the structure or function of the brain. But there are a
couple of problems with this.”
One problem is, quite simply, a
mouse is not a human. There are many human-specific features that scientists
can only study in the human brain.
“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.”
Genes contain DNA, the basic human
code that, when translated into action, creates proteins that “do” things, such
as help your finger muscles type or your heart beat or your liver process
toxins. But only about 3 percent of the human genome codes for proteins. The
vast majority of the human genome is called the noncoding genome. Much of this
region is not shared between mice and humans. This noncoding genome consists of
tiny molecular switches that can modulate the expression of other genes. These
switches don’t directly alter the function of a protein, but they can affect
the amounts of a protein that is expressed. Turns out, most genetic variants
associated with psychiatric disorders are found in the noncoding region of the
genome.
These findings can now be a resource
for scientists to help answer important questions about the genetic influences
on the brain and how they relate to numerous conditions.
Source: http://news.unchealthcare.org/news/2020/march/worldwide-study-unlocks-genetic-secrets-of-gray-matter
Journal
article: https://science.sciencemag.org/content/367/6484/eaay6690
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