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Genetic Variants Build a Smarter Brain

19 June 2012 5:00 pm
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Paul Thompson/UCLA

Brain gain. Brain scan data showing regions where two of the newly identified SNPs interact with each other to affect white matter tract integrity.

Researchers have yet to understand how genes influence intelligence, but a new study takes a step in that direction. An international team of scientists has identified a network of genes that may boost performance on IQ tests by building and insulating connections in the brain.

Intelligence runs in families, but although scientists have identified about 20 genetic variants associated with intelligence, each accounts for just 1% of the variation in IQ scores. Because the effects of these genes on the brain are so subtle, neurologist Paul Thompson of the University of California, Los Angeles, devised a new large-scale strategy for tackling the problem. In 2009, he co-founded the ENIGMA Network, an international consortium of researchers who combine brain scanning and genetic data to study brain structure and function.

Earlier this year, Thompson and his colleagues reported that they had identified genetic variants associated with head size and the volume of the hippocampus, a brain structure that is crucial for learning and memory. One of these variants was also weakly associated with intelligence. Those carrying it scored on average 1.29 points better on IQ tests than others, making it one of the strongest candidate intelligence genes so far.

The researchers have now used the same strategy to identify more genetic variants associated with brain structure and IQ. In the new study, they analyzed brain images and whole-genome data from 472 Australians, including 85 pairs of identical twins, 100 pairs of nonidentical twins, and their nontwin siblings. They identified 24 genetic variations within six different genes, all of which were linked to differences in the structural integrity of major brain pathways. "We measured the insulation of the neural pathways," says Thompson. "This affects how fast nervous impulses are routed around the brain. If the pathways are insulated poorly, the brain functions less efficiently and is less resistant to disease."

Many of the genes were already known, but "most haven't been linked to brain integrity before," says Thompson. He adds that the genes "help to make cell membranes and connections" in pathways that are involved in spatial abilities and working memory, which allows us to store information for short periods of time while performing mental tasks.

The researchers also found that some of the variants are associated with intelligence, in that individuals carrying them performed several points better on standardized IQ tests than others. The variants seem to amplify each other's effects, so that possessing more than one provided a synergistic IQ boost, the team reports online today in the Journal of Neuroscience. "We found a whole range of genetic variants that affect the impact of other variants," says Thompson, "and we are beginning to understand the guiding principles of these gene networks."

The researchers used a "highly sophisticated method" that simplifies the statistics involved by identifying gene networks rather than individual variants, says human geneticist Silvia Paracchini of the University of St. Andrews in the United Kingdom, who was not involved in the study.

She questions how robustly the experiments were designed, however, and says that the number of participants was relatively small for a study of this kind. "I would like to see the findings replicated, with further evidence from larger samples."

Epidemiologist Sarah Medland of the Queensland Institute of Medical Research in Australia adds another note of caution: Most large-scale genetic studies replicate their findings using preexisting sets of data, Medland says, but "There was no replication here." But that may be because there are no other appropriate data sets. Medland says she knows of only one other study that collected both IQ scores and the same kind of brain imaging data, and that "the data probably aren't comparable."

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