Autism linked primarily to common gene variants

The main cause of autism disorders isn't environmental influences or DNA mutations but the inheritance of certain common gene variants, according to a study based on data from an unprecedentedly large population sample.

Data from millions of Swedes studied to assess risk factors

Children with autism spectrum disorder are sometimes non-verbal and can require constant care. A new study suggests the single largest risk factor for developing the condition is having a number of common, inherited gene variants. (Nati Harnik/Associated Press)

The main cause of autism disorders isn't environmental influences or DNA mutations but the inheritance of certain common gene variants, according to a study based on data from an unprecedentedly large population sample.  

The research addresses a question that has bedevilled scientists for decades — namely, what causes the range of ailments known as autism spectrum disorder. People with autism often experience a lack of social and communication skills, exhibit ritualistic physical activity and sometimes have a vast intelligence on particular subjects.

Various studies over the years have pegged the genetic influence on whether someone develops an autism disorder at anywhere from under 20 per cent to 90 per cent of the risk.

The latest research suggests genetics are the single greatest factor in whether someone develops the condition, accounting for about half of the cause.

Crucially, though, according to the study from Swedish and American scientists, most of the genes underlying autism disorders aren't beset by rare mutations, but are common variants found in the general population.  

"Although each exerts just a tiny effect individually, these common variations in the genetic code add up to substantial impact, taken together," study co-author Joseph Buxbaum, a professor of medicine at Mount Sinai medical school in New York City, said in a statement.

That represents a change in thinking from early genetic studies of the condition, which focused on rare glitches in the DNA of people with autism disorders.

Millions of records

In the new study, published online Sunday in the journal Nature Genetics, researchers looked at 466 Swedish people with autism and 2,580 others as controls.

They were also able to draw on a massive database that included information on all children born in Sweden between 1982 and 2007. It was made possible because of Sweden's universal registry of health records. The database permitted scientists to assess the genetic risks of autism by looking at data on millions of siblings and cousins, as well as tens of thousands of twins.  

Applying statistical analyses, the study concludes that 49 per cent of someone's susceptibility for autism stems from common inherited variations in their genes, while a further three per cent is due to rare, inherited variants. A further 2.6 per cent of the risk of developing autism comes from rare and spontaneous mutations arising in a person's own DNA.

"Although uncertainty is inherent in all of these estimates, the results converge on a total heritability in the range of 50 to 60 per cent, with common variants explaining the bulk of it," the study says.

The next step for researchers is to identify the exact genetic variants that contribute to autism spectrum disorder, or ASD, and which spontaneous mutations in particular underpin it.

"Within a given family, the mutations could be a critical determinant that leads to the manifestation of ASD in a particular family member," Buxbaum said in the statement.

"The family may have common variation that puts it at risk, but if there is also a de novo [spontaneous] mutation on top of that, it could push an individual over the edge."

Researchers at the Sick Kids Hospital in Toronto have done similar work looking into the relative influence of inherited versus spontaneously mutated genetic variations on autism spectrum disorder. 


To encourage thoughtful and respectful conversations, first and last names will appear with each submission to CBC/Radio-Canada's online communities (except in children and youth-oriented communities). Pseudonyms will no longer be permitted.

By submitting a comment, you accept that CBC has the right to reproduce and publish that comment in whole or in part, in any manner CBC chooses. Please note that CBC does not endorse the opinions expressed in comments. Comments on this story are moderated according to our Submission Guidelines. Comments are welcome while open. We reserve the right to close comments at any time.