DNA Variants That Cause Poor Health May Also Make You ‘Stupid’
What makes some people smarter than others? A genetic analysis of families in Scotland, UK, hints that brainier people have fewer DNA mutations that impair intelligence and general health, rather than having more genetic variants that make them smarter.
“This is one of the most exciting studies on the genetics of intelligence I’ve seen for a while,” says Steve Stewart-Williams of the University of Nottingham Malaysia Campus, who was not involved in the work.
One implication is that using gene editing to fix the hundreds of mutations that slightly damage people’s health would make them smarter as well as healthier. “I think this strengthens the moral case for pursuing genome editing technologies,” says ethicist Christopher Gyngell of the University of Oxford. “It would be killing two birds with one stone, and that would be a good thing.”
There is no doubt that intelligence depends partly on the environment in which we grow up. Well-nourished children brought up in safe, unpolluted and stimulating environments on average score better in IQ tests than deprived children, for instance.
But our genes also play a role. Studies of twins have suggested that 50 to 80 per cent of the variation in general intelligence between people could be down to genes. However, finding the gene variants responsible for intelligence has proven tricky.
So far, studies of the DNA of hundreds of thousands of unrelated people suggest that only around 30 per cent of the variation in intelligence is inherited. This big discrepancy between the results of twin studies and genome studies has become known as the mystery of the missing heritability.
Now a team including David Hill of the University of Edinburgh, UK, has analysed data from 20,000 people taking part in a study called Generation Scotland, which is looking at the health and genomes of families. The team used a statistical method to work out how much effect rare genetic variants shared by most of the members of a family have on intelligence. Because these variants are so rare in unrelated people, other studies have missed their effect.
They found that rare genetic variants missed by other studies explain the discrepancy between the two types of study. “If the result stands up, they’ve solved the missing heritability problem for intelligence,” says Stewart-Williams. “Pretty impressive.”
The findings help us understand how our genomes determine intelligence. In theory, smart people may be that way because they have beneficial variants of genes that boost IQ. But we would expect beneficial gene variants to spread by natural selection, becoming common in a population. Hill’s findings suggest an important role for very rare gene variants. These are more likely to be slightly harmful mutations that also impair health. Evolution isn’t very good at getting rid of such mutations, so they build up, creating a “mutational load” that varies from person to person. The findings suggest people’s intelligence depends on their mutational load, says Rosalind Arden of the London School of Economics, who studies intelligence and genetics.
Attempts to link intelligence to genes are controversial – many people do not like the idea that IQ is mostly determined by a person’s DNA. But Arden argues that genetic influence on intelligence is a good thing. “If intelligence differences were all environmental, that would be absolutely catastrophic,” she says. If that was the case, all those raised in deprived circumstances would be less intelligent than those from more privileged backgrounds, which would make societies even more unequal than they are now.
Smarter people tend to be healthier and live longer, although it’s not yet clear why. Intelligent people may be more likely to live a better lifestyle, but Hill’s study suggest they are also genetically healthier too.
We are still some way from using techniques like CRISPR to edit the genomes of our embryos, but some believe it’s inevitable we will one day take this step, and expert reports in countries including the US and UK have been suggested it could be used to prevent diseases.
If Hill’s findings hold up in further studies, it suggests that attempts to remove mutations that are slightly harmful for health should also raise intelligence. “We’re not talking about making people way, way smarter than the smartest people today – it’s just bringing the average up,” says Gyngell.
Journal reference: bioRxiv, DOI: 10.1101/106203
Michael Le Page