Autism-related genes linked to cognitive ability

Wednesday March 11 2015

"Autism is linked to higher intelligence," the Mail Online reports. A new study found evidence that certain genetic variations associated with autistic spectrum disorder (ASD) were linked to greater cognitive ability in non-autistic individuals.

Researchers looked at the DNA of more than 10,000 people in the general population in Scotland and Australia. The study aimed to see whether genetic variations associated with ASD are associated with improved cognitive ability in the general population. They carried out a similar assessment for variants associated with attention deficit hyperactivity disorder (ADHD).

They found that individuals carrying more of the genetic variations associated with ASD had slightly higher overall cognitive scores. No consistent link was found between ADHD-associated variants and improved cognitive performance.

The most important thing to know about these results is that the effect seen was very small. Less than 0.5% of the difference seen in people’s cognitive scores was explained by how many of the ASD-linked genetic variants they carried. These findings would need to be replicated in other, larger, samples to be confirmed.

These findings do not currently have any obvious practical implications for individuals.

Where did the story come from?

The study was carried out by researchers from the University of Edinburgh and other research centres in the UK and Australia. The study received its main funding from the Chief Scientist Office of the Scottish Government Health Directorates and the Scottish Funding Council, Age UK and the Biotechnology and Biological Sciences Research Council (BBSRC), and the researchers and centres had various other sources of funding.

The study was published in the peer-reviewed journal Molecular Psychiatry.

The Mail Online's reporting could give readers the impression the improvement in cognitive ability seen by the researchers is much more impressive than it actually was.

It is only towards the end of the article that the website provides a quote from one of researchers pointing out that the variants only provided a "small intellectual advantage".

What kind of research was this?

This was a cross sectional study looking at whether genetic variations associated with autism spectrum disorders (ASD) or attention deficit hyperactivity disorder (ADHD) are associated with cognitive ability in the general population.

The researchers report that individuals with ADHD and ASD often have cognitive difficulties, although the relationship is more complex for ASD. The researchers say that some studies have found better cognitive functioning on some tests in individuals with ASD than controls.

While some diseases, such as cystic fibrosis, are caused by mutations in a single gene, the genetic contribution to other conditions such as ASD and ADHD is more complex and not fully understood. Rather than a single gene, variations in a large number of genes are thought to each contribute to increasing a person’s risk. These genetic variations are common in the population, and most people who carry them will not have ASD or ADHD. Cognitive ability also appears to have a complex genetic component.

The researchers in the current study wanted to see whether the genetic variants that have been linked to ASD or ADHD are linked to cognitive ability in the general population. If so, this might suggest that the same genes are contributing to ASD and ADHD, as well as cognitive function.

What did the research involve?

The researchers analysed the DNA of 9,863 Scottish individuals, who had also completed cognitive tests. They looked for a range of common genetic variations that have been found to be linked with ASD or ADHD. They analysed whether the number of these variations a person had was related to their cognitive performance.

The participants were taking part in the Generation Scotland: Scottish Family Health Study. The participants completed four cognitive tests:

  • the Mill Hill vocabulary scale junior and senior synonym test – where participants are asked to explain the meaning of certain words
  • a test of verbal declarative memory (logical memory) – where participants are asked to recall a series of previous learned facts and events
  • the Wechsler digit symbol substitution task – where participants are given a list of digit-symbol pairs (such as # = 14) and then translate a list of symbols into digits as fast as possible
  • a verbal fluency test – where participants are asked to say as many words from a category in a given time – such as "how many animals beginning with the letter E can you name in 60 seconds"

The researchers combined the results of these tests, to obtain a measure of performance across them all. For each participant, the researchers calculated a genetic "risk score" based on how many of the ASD or ADHD-linked genetic variants they had. They then carried out statistical analyses to see if there were links between a person’s genetic "risk score" and cognitive performance. They took into account people’s age and gender in the analyses.

The researchers also repeated their analyses on two other samples of people – one from Scotland (1,522 people) and one from Australia (921 people) – to see if they got the same results. This second Scottish sample had cognitive tests in childhood and old age, and the Australian sample had cognitive tests in adolescence. Different cognitive tests were used in the three samples.

What were the basic results?

The researchers found that having a higher genetic risk score for ASD was linked with having a slightly higher overall cognitive performance score in their large Scottish sample. A higher genetic risk score for ASD was also linked with having a slightly higher score on three of the four individual cognitive tests (logical memory, vocabulary test and verbal fluency test). A one unit increase in genetic risk score was associated with between a 0.04 and 0.07 unit increase in each of these scores. These were small effects, and variation in the genetic risk score accounted for less than 0.5% of the variation in people’s scores.

The researchers found similar associations between genetic risk score for ASD and different cognitive tests in the Australian sample, but did not find associations for their second, smaller Scottish sample.

When looking at the genetic risk score for ADHD, the researchers found no associations with cognitive performance in the main Scottish sample or the Australian sample. There was an association between higher genetic risk score for ADHD and slightly lower IQ score at age 11 in the second (smaller) Scottish sample. A one unit increase in genetic risk score was associated with a 0.08 unit reduction in this score. Other measures of cognitive performance in this study did not show consistent associations with ADHD genetic risk score.

How did the researchers interpret the results?

The researchers concluded that their findings suggest common genetic variants linked to ASD are also associated with general cognitive ability in general population.

Conclusion

This study has found some small associations between common genetic variations linked to ASD and cognitive performance in the general population.

Even where an association was found between genetic risk score and cognitive performance, the effect was very small. Less than 0.5% of the variability in people’s cognitive scores in the main study sample was explained by their ASD genetic risk score.

The link between ASD genetic risk score and cognitive performance were only found in two of the three population samples assessed. This may be due to different age groups of participants, or to different cognitive tests being used. There was even less consistency in findings relating to ADHD genetic risk score. Ideally these findings need to be replicated in other, larger, samples to confirm them.

The study is likely to be of interest to researchers, but does not have any obvious practical implications for individuals.

Analysis by Bazian
Edited by NHS Choices