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Best evidence yet that a single gene can affect IQ
THIS WEEK
Andy Coghlan
SOVEREIGN, ISM/SCIENCE PHOTO LIBRARY
Single gene affects IQ – but only just to some researchers, the finding is de facto proof that intelligence relies on the action of a multitude of genes after all. HMGA2 has previously been linked with people’s height. The IQ difference shows up in a mutation of the gene in which a single DNA “letter” is changed from C (cytosine) to T (thymine). “C is the good one,” says Thompson. As well as raising IQ by 1.29, it increases the overall volume of the brain by 0.58 per cent of average brain size. “It’s a loss or gain of about 2 teaspoons,” he says.
IT’S the exception that proves the rule. A massive genetics study involving over 21,000 people has revealed the best evidence yet that a single gene can raise IQ – but the effect is so small that it leaves intact the idea that variations in intelligence depend on the effects of hundreds of genes. There is little dispute that genetics accounts for a large amount of the variation in people’s intelligence, but studies have consistently failed to find any single genes that have a “It took a sample of 21,000 substantial impact. people to find the gene’s That has now changed, effect, precisely because following a brain study on an the effect is so small” unprecedented scale designed to probe the links between genetics and some brain diseases (see The team took DNA samples “Brain-drain genes”, below). from 21,151 adults and also Variation in a single gene, called scanned each volunteer’s brain HMGA2, has a measurable effect to look for size differences. It was on intelligence – although the the brain-size-altering effect of gene alters IQ by just 1.29 points. HMGA2 that led the researchers “It seems like the biggest to study its impact on IQ. single-gene impact we know of They looked in more detail at that affects IQ. But it’s not a a subset of 1642 volunteers from a massive effect on IQ overall,” says twin study in Brisbane, Australia, Paul Thompson at the University who had all taken standard IQ tests. of California, Los Angeles, who From that analysis, they discovered led the collaboration of 207 the 1.29 point rise associated with researchers. Indeed, according HMGA2’s C-variant. If people
–Intelligence is a team effort–
inherit that variant from both parents they have double the effect: a rise in IQ of about 2.6 (Nature Genetics, DOI: 10.1038/ ng.2250). “It’s important they’ve found this gene, but it took a sample of 21,000 people to find it, precisely because the effect is so small,” says Robert Plomin at the Institute of Psychiatry in London, who was lead author of a groundbreaking study in 2007 which failed to find any single genes of disproportionate
Brain-drain genes It was brain diseases rather than IQ that encouraged Paul Thompson at the University of California, Los Angeles, and colleagues to amass data on more than 21,000 volunteers. Thompson’s team discovered that the gene HMGA2 alters brain size by up to 0.58 per cent. Meanwhile a variant of another gene, TESC, can change the size of the hippocampus by up to 1.2 per cent. This learning and memory hub of the brain is
14 | NewScientist | 21 April 2012
known to be ravaged in Alzheimer’s disease. Given that the adult hippocampus shrinks by around 0.5 per cent per year, those people in which TESC results in a hippocampus 1.2 per cent smaller than average have effectively experienced more than two years of premature ageing, a factor that could accelerate disease. A second major study using the same data set found other genes that reduce hippocampus size. A gene
called harakiri controls cell death via apoptosis, so it may be that a faulty variant of it kills off some healthy cells. The other risky variant is of a gene called MSR3B (Nature Genetics, DOI: 10.1038/ng.2237). “Having one copy of [either] risk variant had the same effect on hippocampal size as four to five years of ageing,” says lead author of the study, Sudha Seshadri of Boston University.
importance in intelligence. He says the new study confirms that the hunt for genes with a bigger impact on IQ is likely to fail. “If it’s this hard to find an effect of just 1 per cent, what you’re really showing is that the ‘cup’ is 99 per cent empty.” Steven Pinker, a professor of neuropsychology at Harvard University, agrees. “It’s an important finding, assuming it holds up,” he says. Pinker says that geneticists have had trouble finding single genes that cause large differences in traits that we know to be highly heritable, such as height – a problem known as the paradox of missing heritability. “We’ve always suspected that there are two resolutions of the paradox. One is that heritable traits are affected by large numbers of genes, each with a tiny effect. The other is that there are genes with moderate or large effects but they are highly uncommon,” he says. “The Thompson study is a first step in showing that at least the first alternative is true in the case of intelligence.” n
Andy Coghlan
SOVEREIGN, ISM/SCIENCE PHOTO LIBRARY
Single gene affects IQ – but only just to some researchers, the finding is de facto proof that intelligence relies on the action of a multitude of genes after all. HMGA2 has previously been linked with people’s height. The IQ difference shows up in a mutation of the gene in which a single DNA “letter” is changed from C (cytosine) to T (thymine). “C is the good one,” says Thompson. As well as raising IQ by 1.29, it increases the overall volume of the brain by 0.58 per cent of average brain size. “It’s a loss or gain of about 2 teaspoons,” he says.
IT’S the exception that proves the rule. A massive genetics study involving over 21,000 people has revealed the best evidence yet that a single gene can raise IQ – but the effect is so small that it leaves intact the idea that variations in intelligence depend on the effects of hundreds of genes. There is little dispute that genetics accounts for a large amount of the variation in people’s intelligence, but studies have consistently failed to find any single genes that have a “It took a sample of 21,000 substantial impact. people to find the gene’s That has now changed, effect, precisely because following a brain study on an the effect is so small” unprecedented scale designed to probe the links between genetics and some brain diseases (see The team took DNA samples “Brain-drain genes”, below). from 21,151 adults and also Variation in a single gene, called scanned each volunteer’s brain HMGA2, has a measurable effect to look for size differences. It was on intelligence – although the the brain-size-altering effect of gene alters IQ by just 1.29 points. HMGA2 that led the researchers “It seems like the biggest to study its impact on IQ. single-gene impact we know of They looked in more detail at that affects IQ. But it’s not a a subset of 1642 volunteers from a massive effect on IQ overall,” says twin study in Brisbane, Australia, Paul Thompson at the University who had all taken standard IQ tests. of California, Los Angeles, who From that analysis, they discovered led the collaboration of 207 the 1.29 point rise associated with researchers. Indeed, according HMGA2’s C-variant. If people
–Intelligence is a team effort–
inherit that variant from both parents they have double the effect: a rise in IQ of about 2.6 (Nature Genetics, DOI: 10.1038/ ng.2250). “It’s important they’ve found this gene, but it took a sample of 21,000 people to find it, precisely because the effect is so small,” says Robert Plomin at the Institute of Psychiatry in London, who was lead author of a groundbreaking study in 2007 which failed to find any single genes of disproportionate
Brain-drain genes It was brain diseases rather than IQ that encouraged Paul Thompson at the University of California, Los Angeles, and colleagues to amass data on more than 21,000 volunteers. Thompson’s team discovered that the gene HMGA2 alters brain size by up to 0.58 per cent. Meanwhile a variant of another gene, TESC, can change the size of the hippocampus by up to 1.2 per cent. This learning and memory hub of the brain is
14 | NewScientist | 21 April 2012
known to be ravaged in Alzheimer’s disease. Given that the adult hippocampus shrinks by around 0.5 per cent per year, those people in which TESC results in a hippocampus 1.2 per cent smaller than average have effectively experienced more than two years of premature ageing, a factor that could accelerate disease. A second major study using the same data set found other genes that reduce hippocampus size. A gene
called harakiri controls cell death via apoptosis, so it may be that a faulty variant of it kills off some healthy cells. The other risky variant is of a gene called MSR3B (Nature Genetics, DOI: 10.1038/ng.2237). “Having one copy of [either] risk variant had the same effect on hippocampal size as four to five years of ageing,” says lead author of the study, Sudha Seshadri of Boston University.
importance in intelligence. He says the new study confirms that the hunt for genes with a bigger impact on IQ is likely to fail. “If it’s this hard to find an effect of just 1 per cent, what you’re really showing is that the ‘cup’ is 99 per cent empty.” Steven Pinker, a professor of neuropsychology at Harvard University, agrees. “It’s an important finding, assuming it holds up,” he says. Pinker says that geneticists have had trouble finding single genes that cause large differences in traits that we know to be highly heritable, such as height – a problem known as the paradox of missing heritability. “We’ve always suspected that there are two resolutions of the paradox. One is that heritable traits are affected by large numbers of genes, each with a tiny effect. The other is that there are genes with moderate or large effects but they are highly uncommon,” he says. “The Thompson study is a first step in showing that at least the first alternative is true in the case of intelligence.” n