Scientists tie 52 genes to human intelligence

The findings may lead to new experiments into the biological basis of reasoning and problem-solving, experts say

Image Credit: Wellcome Trust via NYT
In an undated handout photo, blood samples from some participants in a new study of genes linked to intelligence, at the UK Biobank.
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In a significant advance in the study of mental ability, a team of European and American scientists announced last Monday that they had identified 52 genes linked to intelligence in nearly 80,000 people.

These genes do not determine intelligence, however. Their combined influence is minuscule, the researchers said, suggesting that thousands more are likely to be involved and still await discovery. Just as important, intelligence is profoundly shaped by the environment.

Still, the findings could make it possible to begin new experiments into the biological basis of reasoning and problem-solving, experts said. They could even help researchers determine which interventions would be most effective for children struggling to learn.

“This represents an enormous success,” said Paige Harden, a psychologist at the University of Texas, who was not involved in the study.

For over a century, psychologists have studied intelligence by asking people questions. Their exams have evolved into batteries of tests, each probing a different mental ability, such as verbal reasoning or memorisation.

In a typical test, the tasks might include imagining an object rotating, picking out a shape to complete a figure, and then pressing a button as fast as possible whenever a particular type of word appears.

Each test-taker may get varying scores for different abilities. But overall, these scores tend to hang together — people who score low on one measure tend to score low on the others, and vice versa. Psychologists sometimes refer to this similarity as general intelligence.

It’s still not clear what in the brain accounts for intelligence. Neuroscientists have compared the brains of people with high and low test scores for clues, and they’ve found a few.

Brain size explains a small part of the variation, for example, although there are plenty of people with small brains who score higher than others with bigger brains.

Other studies hint that intelligence has something to do with how efficiently a brain can send signals from one region to another.

Danielle Posthuma, a geneticist at Vrije University Amsterdam and senior author of the new paper, first became interested in the study of intelligence in the 1990s. “I’ve always been intrigued by how it works,” she said. “Is it a matter of connections in the brain, or neurotransmitters that aren’t sufficient?”

Posthuma wanted to find the genes that influence intelligence. She started by studying identical twins who share the same DNA. Identical twins tended to have more similar intelligence test scores than fraternal twins, she and her colleagues found.

Hundreds of other studies have come to the same conclusion, showing a clear genetic influence on intelligence. But that doesn’t mean that intelligence is determined by genes alone.

Our environment exerts its own effects, only some of which scientists understand well. Lead in drinking water, for instance, can drag down test scores. In places where food doesn’t contain iodine, giving supplements to children can raise scores.

Advances in DNA sequencing technology raised the possibility that researchers could find individual genes underlying differences in intelligence test scores. Some candidates were identified in small populations, but their effects did not reappear in studies on larger groups.

So scientists turned to what’s called the genome-wide association study: They sequence bits of genetic material scattered across the DNA of many unrelated people, then look to see whether people who share a particular condition — say, a high intelligence test score — also share the same genetic marker.

In 2014, Posthuma was part of a large-scale study of more than 150,000 people that revealed 108 genes linked to schizophrenia. But she and her colleagues had less luck with intelligence, which has proved a hard nut to crack for a few reasons.

Standard intelligence tests can take a long time to complete, making it hard to gather results on huge numbers of people. Scientists can try combining smaller studies, but they often have to merge different tests together, potentially masking the effects of genes.

As a result, the first generation of genome-wide association studies on intelligence failed to find any genes. Later studies managed to turn up promising results, but when researchers turned to other groups of people, the effect of the genes again disappeared.

But in the past couple years, larger studies relying on new statistical methods finally have produced compelling evidence that particular genes really are involved in shaping human intelligence.

“There’s a huge amount of real innovation going on,” said Stuart J. Ritchie, a geneticist at the University of Edinburgh who was not involved in the new study.

Posthuma and other experts decided to merge data from 13 earlier studies, forming a vast database of genetic markers and intelligence test scores. After so many years of frustration, Posthuma was pessimistic it would work.

“I thought, ‘Of course we’re not going to find anything’,” she said.

She was wrong. To her surprise, 52 genes emerged with firm links to intelligence. A dozen had turned up in earlier studies, but 40 were entirely new.

But all of these genes together account for just a small percentage of the variation in intelligence test scores, the researchers found; each variant raises or lowers IQ by only a small fraction of a point.

“It means there’s a long way to go, and there are going to be a lot of other genes that are going to be important,” Posthuma said.

Christopher F. Chabris, a co-author of the new study at Geisinger Health System in Danville, Pennsylvania, was optimistic that many of those missing genes would come to light, thanks to even larger studies involving hundreds of thousands, perhaps millions, of people.

“It’s just like astronomy getting better with bigger telescopes,” he said.

In the new study, Posthuma and her colleagues limited their research to people of European descent because that raised the odds of finding common genetic variants linked to intelligence.

But other gene studies have shown that variants in one population can fail to predict what people are like in other populations. Different variants turn out to be important in different groups, and this may well be the case with intelligence.

“If you try to predict height using the genes we’ve identified in Europeans in Africans, you’d predict all Africans are 5 inches shorter than Europeans, which isn’t true,” Posthuma said.

Studies like these don’t mean that intelligence is fixed by our genes, experts noted. “If we understand the biology of something, that doesn’t mean we’re putting it down to determinism,” Ritchie said.

As an analogy, he noted that nearsightedness is strongly influenced by genes. But we can change the environment — in the form of eyeglasses — to improve people’s eyesight.

Harden predicted that an emerging understanding of the genetics of intelligence would make it possible to find better ways to help children develop intellectually. Knowing people’s genetic variations would help scientists measure how effective different strategies are.

Still, Harden said, we don’t have to wait for such studies to change people’s environments for the better. “We know that lead harms children’s intellectual abilities,” she said. “There’s low-hanging policy fruit here.”

For her part, Posthuma wants to make sense of the 52 genes she and her colleagues discovered. There are intriguing overlaps between their influence on intelligence and on other traits.

The genetic variants that raise intelligence also tend to pop up more frequently in people who have never smoked. Some of them also are found more often in people who take up smoking but quit successfully.

As for what the genes actually do, Posthuma can’t say. Four of them are known to control the development of cells, for example, and three do an assortment of things inside neurons.

To understand what makes these genes special, scientists may need to run experiments on brain cells. One possibility would be to take cells from people with variants that predict high and low intelligence.

She and her colleagues might coax them to develop into neurons, which could then grow into “mini-brains” — clusters of neurons that exchange signals in the laboratory. Researchers could then see if their genetic differences made them behave differently.

“We can’t do it overnight,” Posthuma said, “but it’s something I hope to be able to do in the future.”

–New York Times News Service