In one of the largest-ever studies of genetics and autism, researchers have identified 24 new gene variants associated with autism spectrum disorders (ASD). The work also confirms that 31 variants previously linked to the developmental disorder may serve as useful genetic markers for identifying those with the condition.
Understanding autism’s genetic roots is a priority, researchers say, since it may lead to earlier diagnosis and behavioral intervention, which can improve patient outcomes.
“Oftentimes findings like this get published in academic journals, but they don’t get translated into clinical use,” says Chuck Hensel, an author on the new research study, published in PLoS ONE, who is the senior manager of research at the genetic diagnostics company Lineagen. “Our goal,” Hensel says, “is to try to get these markers into the clinic.”
Hensel teamed with researchers at the University of Utah and the Children’s Hospital of Philadelphia and devised a two-pronged approach for hunting down genetic markers of autism.
First, the researchers chose 55 people living with autism, all from families with many members diagnosed with ASDs. The scientists then sequenced the genomes of these subjects, and compared the genetic profiles to those from a reference population, using the Utah Genetics Reference Project. That allowed them to find regions where the autistic individuals differed from people without the disorder, and led to 153 gene variants, or genetic red flags for the condition.
But because ASDs occur in a spectrum of mild to severe symptoms, and the genetic contribution of each of these variants likely varied, they needed to find out which of the 153 aberrations were most strongly linked to autism; some were likely indirectly connected to the disorder, and the scientists wanted to weed out those potential red herrings. So Hensel and his collaborators built a new molecular test, or probe, that would identify the 153 variants from a patient sample of blood, as well as for 185 other gene variants that previous studies had linked to autism. Running this probe on genetic samples collected from 2,175 children with clinically diagnosed autism spectrum disorders and also from 5,801 children with normal development, they could compare how well each of the variants matched up with an ASD.
Of the 153 initial candidate gene variants, 15 were confirmed as autism-related. The test also picked up another nine autism-related variants that had never been linked to autism spectrum disorders before. Participants with any of the 24 variants had a two-fold greater risk of developing an ASD than those without the genetic changes.
Of the previously selected 185 genetic variants connected to autism, 31 were also strongly linked with ASDs, but need additional testing to establish how predictive they are of the disorder.
Autism researchers suspect that as many as 200 to 400 genes may be responsible for ASDs, and that patients will exhibit a wide array of diverse genetic combinations of these DNA contributors. Not every person with autism will have each and every autism-related gene variant, but it’s likely that he will show some variation of the genetic changes identified in the study. “The bottom line is that autism simply is a lot of different diseases genetically, each of which gives you a similar behavioral result. But they have different causes,” he says.
And that’s why the findings, as encouraging as they are, still can’t be used to diagnose and identify people at risk of developing autism. However, Hensel hopes that large studies like the current one may start to isolate the true genetic predictors of the condition.
“Because of the size of this study, it really gets us to the cusp of using [genetic markers] clinically,” Hensel says. “We wanted to do a big enough study that we could say, yes, these results really mean something.” And hopefully, within a few years, they will.