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Published on: May 16, 2012
by Alice Park for Time:
Researchers have identified two genes that affect brain size and may be linked not only to IQ, but also to our risk of developing brain disorders like Alzheimer’s disease.
Scientists have known for some time that the size and volume of certain parts of the brain are linked to disorders including developmental conditions such as autism and degenerative diseases like Alzheimer’s. The brains of autistic children, for example, tend to be bigger than those of unaffected youngsters, and in Alzheimer’s patients, the brain region responsible for memory, the hippocampus, tends to be smaller.
But what influences brain size to begin with? It’s a feature that is highly heritable among humans, suggesting that genes may play a role. That suggests in turn that such genes may also influence vulnerability to any number of mental disorders that are linked to brain size, above and beyond the genes that directly affect memory or language skills, for example.
So researchers involved in the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium — more than 200 scientists from 100 institutions worldwide — decided to figure out which genes are responsible for brain size (with the assumption that they would then predispose people to brain disorders) by combining two powerful techniques: genome-wide analyses of disease-related genetic variants and brain imaging.
The researchers looked at MRI scans of the brain structures of 21,000 people, both with disorders including depression, anxiety, Alzheimer’s and schizophrenia, or without these conditions and compared them to genetic surveys of the DNA changes linked to these disorders.
Even the researchers were surprised by how well the strategy worked: they found two genetic variants, one that appears to be associated with overall brain size and another that was linked to the volume of the hippocampus, or memory center, which typically shrinks in people with dementia.
“None of these changes on their own will give you disease,” says the study’s senior author, Paul Thompson, professor of neurology and psychiatry at UCLA Medical School, of the group’s findings, published in Nature Genetics. “But they vastly tilt the scales in favor of disease.”
People who had the genetic variant associated with smaller hippocampus volumes had shrinkage equivalent to about five years of aging, Thompson said, meaning that whatever degradation in brain functions — memory, learning or attention — that occur with aging would be accelerated. That’s even after accounting for the known factors that can affect brain volumes, including ethnicity, height and other physical attributes.
One copy of the gene variant conferred a 1.3% reduction in hippocampal volume, while two copies, one from each parent, doubled that shrinkage. With normal aging, the brain loses about 0.5% of tissue a year, but the variant that Thompson and his colleagues discovered sped up that process considerably, potentially making the person more vulnerable to developing age-related disorders, including Alzheimer’s.
“We know what the variant of this gene looks like — the carriers of this new gene look like their brains are five years older than they should be,” says Thompson. “This is a major genetic discovery that makes that much of a difference on a brain scan. We don’t yet know whether the loss of tissue tilts the sales to people to have increased risk of Alzheimer’s disease, but it gives you a very strong lead.”
The other variant the team isolated was related to overall brain volume and was linked to a 1.3-point change in IQ. The effect of the gene on IQ scores was small, but significant — enough to show up on an IQ test. However, the authors note that there are many contributors to brain size and IQ, such as a good education, exercise and other environmental factors, which would outweigh the effect of this single gene variant.
The idea is to use these two variants as a starting point for thinking about how to improve diagnosis and eventually treatment of brain disorders, says Thompson. With Alzheimer’s, for example, experts believe that people can use brain-boosting techniques like exercise, continuing education and social interaction to reinforce existing nerve networks and build up a cognitive reserve — like a savings account for the brain. As the brain’s networks start to deteriorate naturally with age, it can call on its reserves to compensate for the loss of tissue and still function reasonably well.
People with the genetic variants isolated in the ENIGMA study, however, may have a smaller reserve due to their genetically influenced brain structures, and may therefore be more vulnerable to any environmental factors, such as obesity or excessive alcohol consumption, that further reduces brain volumes. “We all experience slow erosion of the brain by an army of culprits,” says Thompson. “And that army includes your genes. The relief platoon includes how much you invest in exercise, a good diet and education. So those two forces are basically in opposition.”
What’s encouraging about the results is that they hint that brain scans can be a powerful indicator of gene activity, or a way of tracking how certain genes are functioning and possibly contributing to disease — well before any symptoms appear. “These findings are a very, very big lead for brain health,” says Thompson, “and they can help our understanding of what we might do to prevent brain decline.”
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