USC researchers lead an international team identifying seven genes that predict ‘intracranial volume’ and Parkinson’s disease
USC scientists are beginning to crack the brain’s genetic code, discovering how variations in DNA affect the structure of our brains. (Photo/Paul Thompson/ENIGMA)
In
the world’s largest MRI study on brain size to date, USC researchers and their
international colleagues identified seven genetic hotspots that regulate brain
growth, memory and reasoning as well as influence the onset of Parkinson’s
disease.
Most
brain imaging studies evaluate around 100 people, but the Nature
Neuroscience study
published on Oct. 3 examined 32,438 adults, said Paul Thompson, a corresponding
author and associate director of the USC Mark and
Mary Stevens Neuroimaging and Informatics Institute. The results
bring scientists closer to understanding the genetic program that builds the
living brain.
“Brain
measures from MRI account for about 15 percent of the differences in our
cognitive ability — that is, brain-based skills required to perform simple and
complex tasks,” said Thompson, who led a team of more than 300 international
scientists. “The genes underlying brain development have far-reaching effects
that extend well beyond the initial years of life. You have genes that are
beneficial for you and help build brain structures early in life. Yet some of
these are harmful later in life and promote diseases such as Parkinson’s.”
Parkinson’s
disease is a progressive disorder of the nervous system that affects movement
and often leads to tremors. Like many other degenerative brain disorders, a
cure does not yet exist.
Although
scientists have not determined an ideal healthy brain size, a brain that is too
small (microcephaly) or too big (macrocephaly) can lead to abnormal cognitive development
and lifelong challenges. The human brain reaches maximum size around a person’s
early 20s, Thompson said.
The
study used data on subjects from 52 study sites that are part of the Cohorts
for Heart and Aging Research in Genomic Epidemiology consortium and Enhancing
Neuro Imaging Genetics through Meta Analysis (ENIGMA) consortium, which is
based at USC and led by Thompson. The research supports the notion that brain
size could be used as a measure of “brain reserve,” meaning brain size can
promote resilience to age-related brain diseases.
ENIGMA
is part of the USC Mark and Mary Stevens Neuroimaging and Informatics
Institute, which aims to enhance discovery through the application of imaging
and information techniques in the study of the brain. The institute is a leader
in data acquisition, analysis stewardship and computational innovation for the
purpose of biomedical research.
Genes and environment come into play
Both
genetics and environmental factors affect brain size. Good diet, education and
exercise build a healthy brain in young people and protect older people from
tissue loss.
“This
research is on the leading edge of cracking the brain’s genetic code,” Thompson
said. “Millions of people carry variations in their DNA that help boost or
lower their brains’ susceptibility to a vast range of diseases. Once we
identify these genes, we can target them with drugs to reduce the risk of
disease. People also can take preventive steps through exercise, diet and
mental stimulation to erase the effects of a bad gene.”
The
study began seven years ago. Its technique of using brain scans to identify
gene hotspots provides more information than the traditional method of
collecting DNA samples from patients.
“Now
that we can see a gene’s imprint in brain scans, it’s like capturing a thief
red-handed,” Thompson said. “You can chase it down brain pathways and circuits
and discover what brain cells the gene is damaging. Using brain scans builds a
foundation so that scientists in the future can better focus their studies on
hotspots of interest.”
The seven genes and what they do
Thompson
and his colleagues identified five new gene hubs that predict brain growth and
confirmed two known hotspots. The genes in these areas provide links between an
individual’s maximum brain size and processes such as:
- the production of self-renewing stem cells (FOXO3)
- brain degeneration (MAPT)
- bone density (CENPW)
- physical growth (IGF1, HMGA2)
- DNA replication (GMNC)
- the creation of chemical bonds and proteins (PDCD).
Researchers
adjusted their data for height and confirmed growth predictions by examining
2,824 children from before birth until age 6.
Of
note, one of the areas of the human genome that affects brain size has a normal
version and an inverted alphabet variant that evolved some 3 million years ago,
Thompson said.
“MAPT
is one of the most dangerous genes in this inverted zone,” he said. “It is
implicated in neurodegenerative diseases such as frontotemporal dementia and
Parkinson’s, Alzheimer’s and Lou Gehrig’s disease. Even in the normal
brain-size range, brain scans reveal telltale signs of future disease.”
Ongoing
studies may reveal additional brain conditions that are promoted by the
tau-associated MAPT gene, Thompson said.
“The
genetic program that builds our brains consists of growth factors, cancer
genes, genes that promote dementia and genes that are crucial in helping the
brain to form connections,” Thompson said. “A complex interplay of factors
makes some genes that are beneficial in early life go rogue later in life. It’s
extremely important to understand when genes that affect brain size — such as
the MAPT gene — are helpful and what parts of the brain they are influencing.”
http://news.usc.edu/109149/does-brain-size-really-matter/?
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