TORONTO - The largest ever attempt to compare the DNA of individuals with autism to people without the condition shows a substantial number of rare genetic changes are involved in the development of the disease.
The scientists behind the effort, published online Wednesday by the journal Nature, said the work identifies dozens of new genes involved in autism, with some mutations passing from parents to their autistic offspring and others developing in the autistic individuals themselves.
The pattern that emerges is that the genetic causes of autism are likely far more complex than scientists would have hoped.
Senior investigator Steve Scherer, a leading genetics expert at Toronto's Hospital for Sick Children, says the findings should result in a paradigm shift in the understanding of what causes autism.
"Here our research findings point to the fact that genetic variations that we discovered are actually rare in frequency, meaning most individuals with autism are probably genetically quite unique, each having their own genetic form of autism."
He likened it to each individual having a genetic fingerprint for his or her own version of autism.
An example of the scale of that variability: The findings, based on the study of nearly 1,000 North American and European children with autism spectrum disorders, probably explain about 3.3 per cent of the genetic origins of autism, co-author Dr. Stanley Nelson, professor of human genetics and psychiatry at UCLA, said in a release.
The most common of the genetic changes the scientists spotted was seen in fewer than one per cent of the cases, Scherer said.
The study was done through the International Autism Consortium, and involved 1,500 families and 120 physicians and researchers from 11 countries across North America and Europe.
The main authors seemed undaunted by the complexity of the picture they were painting, even though it dashes hopes that a small number of genetic changes might be responsible for the condition. In theory, few genetic changes might make it easier to develop treatments. In practice, however, therapies for conditions caused by mutation of a single gene can also be elusive.
Cystic fibrosis, for instance, is caused by mutation of a single gene, a fact that was discovered by scientists from Sick Kids Hospital in 1989. But more than 20 years later, that finding has yet to be translated into a gene therapy.
"I think it's been known for a long time that autism clinically is very, very complex, very heterogeneous," Scherer said. "It's almost an artificial grouping of a common clinical endpoint if you will. And this is what the genetics is telling us also."
A welcome part of the findings relates to the fact that the genetic changes appear to cluster along biological pathways, which helps to identify which neurological systems are being affected.
Some of those pathways were previously identified, but this work uncovered others that until now were not implicated in the development of autism.
Another of the lead researchers, Tony Monaco of Oxford University, said knowing the pathways involved should help scientists develop drugs to treat autism or determine if compounds already developed for other conditions might be useful for people with autism.
"There are a lot of drugs that are already developed that are on the shelf for other purposes that could now be tried in autism because we didn't have the knowledge before that these biological pathways were involved," he said.
Other potential implications of the work include the possibility of earlier diagnosis, which in turn would lead to earlier start of the interventions that have been shown to benefit children with autism. Because of the wide variation in genetic changes, coming up with a prenatal test would be difficult, the scientists said.
But they suggested the work could lead eventually allow physicians to predict for parents the form of autism a child was likely to develop and tailor interventions accordingly.
As well, Monaco said, the findings could lead to better genetic counselling on risks for parents who have already had a child with autism.
The study doesn't shed any light on environmental factors that might trigger the genetic changes that lead to autism. But Dr. Geri Dawson, chief science officer of Autism Speaks, said it is believed environmental exposures probably do play a role.
Autism Speaks is an advocacy group that pushes for research into the causes of and possible cures for autism.
But Dawson said there is no evidence to support the debunked yet still repeated claim that vaccines trigger development of the condition.
"I think it's important to underscore the fact that there really is no strong evidence that vaccines play a role in the etiology of autism,'' she said, adding this study points to the strong role genetics play in autism development.