By Dr Ananya Mandal, MD
An international team of researchers have found the genes that increase or reduce the risk of certain mental illnesses and Alzheimer's disease. They claim that some genes that may explain individual differences in brain size and intelligence as well. The team of more than 200 scientists at 100 institutions said this was the largest-ever brain study to date.
“We searched for two things in this study,” senior author Paul Thompson, a professor of neurology at the University of California, Los Angeles David Geffen School of Medicine and a member of UCLA's Laboratory of Neuro Imaging, said in a university news release. “We hunted for genes that increase your risk for a single disease that your children can inherit. We also looked for factors that cause tissue atrophy and reduce brain size, which is a biological marker for hereditary disorders like schizophrenia.
The study researchers measured the size of the brain and its memory centres in thousands of MRI images from more than 21,100 healthy people and screened the participants' DNA at the same time. In people with smaller brains, the researchers found a consistent relationship between subtle differences in the genetic code and smaller memory centres. They also found that the same genes affected the brain in the same ways in people in different populations.
Brain imaging studies are expensive and, as a result, far too small to reliably tease out the effects of common gene variations. These effects tend to be tiny, for one thing, and difficult to distinguish from the background “noise” of other influences.
To solve the numbers problem, Dr. Thompson and three geneticists — Nick Martin and Margaret Wright, both of the Queensland Institute of Medical Research in Australia, and Barbara Franke of the Radboud University Nijmegen Medical Center in the Netherlands — persuaded research centres around the world to pool their resources and create one large database.
As the study was being completed, the Thompson group learned that another consortium, led by Boston University researchers, was doing a similar analysis using its own large group. The two teams’ findings did not completely line up. One found size-related genes that the other did not. But they agreed on two findings: one gene that correlated strongly with overall brain size, and another that correlated with the rate at which the hippocampus atrophies, or shrinks, with age.
The findings may provide new potential targets for drug development. “Millions of people carry variations in their DNA that help boost or lower their brains' susceptibility to a vast range of diseases,” Thompson said. “Once we identify the gene, we can target it with a drug 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 researchers also found that a variant in a gene called HMGA2 may affect brain size and intelligence. “We found fairly unequivocal proof supporting a genetic link to brain function and intelligence. For the first time, we have watertight evidence of how these genes affect the brain. This supplies us with new leads on how to mediate their impact,” Thompson explained.
In a separate analysis in Australia, Dr. Martin and Dr. Wright found that size correlated with I.Q. People with the larger brains scored slightly higher on a standardized test. The results are all averages, meaning that they hold for the group but say nothing about any individual. The collaborators also found that about 10 percent of people carried a gene variant that correlated with a slightly accelerated rate of atrophy in the hippocampus. The hippocampi - there are two, each deep in the brain, one in the right side and one in the left, about level with the ears - are needed to form new memories. People with dementia often show pronounced atrophy in this region. The study was not set up to find a link between the gene variant and dementia, but experts suspect a connection.
The study was published online April 15 in the journal Nature Genetics.
“I like this work a lot, because these guys finally did what needed to be done to take a real stab at merging imaging and genomics,” said Dr. Matthew W. State, a professor of psychiatry at Yale, who was not one of the collaborators.
As a next step Thompson said they will look for clues to disorders such as autism and schizophrenia using diffusion imaging, a new type of brain scan that tracks communication pathways among brain cells.