Genetic analysis from the first 457 families to enroll in SPARK provides new support for several genes linked to autism.
One in ten families that enroll in SPARK get a genetic result, according to analysis of the first 457 families to participate in the project. About 10 percent of participants who have autism have a change in a gene that is strongly linked to autism. Another 3 percent have changes in genes that are likely linked to autism. The results were published in Genomic Medicine in August.
“We are extremely pleased with these results and are hard at work analyzing saliva samples from many more participants, about 5,900 people who have autism and both of their parents,” says Pamela Feliciano, SPARK scientific director. “We have already started returning genetic results to these families and expect to return results to hundreds more.”
SPARK is the largest study of autism, with the goal of enrolling 50,000 people who have autism and their families. To date, more than 36,000 people who have autism have contributed DNA to the project. By the end of 2019 SPARK expects to analyze DNA from about 25,000 people who have autism, with many more thousands to be completed in the next few years.
Scientists estimate that several hundreds of genes likely contribute to autism. A subset of these have already been identified — more than 150 single gene changes and larger-scale changes have strong evidence linking them to autism.
By studying thousands of people, SPARK scientists aim to find the hundreds of genes linked to autism that likely remain unknown and to better understand how specific gene changes contribute to the condition. As more genes that are linked to autism are uncovered, the percentage of families that receive a genetic diagnosis will likely grow as well.
In the first phase of SPARK, known as the pilot study, researchers analyzed data from several hundred families that enrolled between December 2015 and December 2016. The pilot study included 418 families with one child who has autism and 39 families with two or more children who have autism.
Participants who are most likely to get a genetic result are those who have autism along with seizures — 27 percent — or intellectual disability — 20 percent. Families with two or more children who have autism were slightly more likely — 15 percent — to get a genetic result than families with one child who has autism — 10 percent.
Families in the SPARK pilot group had changes in 26 different genes that are linked to autism. Most of these genes had already been strongly linked to autism. However, the SPARK analysis provides new support for several other genes. One of these, called BRSK2, meets the criteria for an autism-risk gene. The list of genes that meet this criteria is updated several times a year based on new research and reviewed by SPARK’s medical genetics committee. More information on how SPARK evaluates autism-risk genes and a full list of genes is available here.
Researchers are also trying to better understand what these genes do. Many of them are important for brain development, including how genes are packaged within brain cells and how brain cells move to the correct location.
Researchers involved with SPARK say the results highlight just how powerful a community of scientists and families can be.
“With just a small piece of the whole SPARK picture, we’ve already identified 9 new autism risk-genes. I know with the 50,000 families we’re working toward we’ll be able to identify so many more,” says Raphael Bernier, executive director of the Seattle Children’s Autism Center and SPARK investigator. “Identifying genes helps us understand how those genes contribute to autism, which will help us target support in a much more precise way. Finally, this project demonstrates how powerful collaborations between scientists, clinicians, and families impacted with autism are.”
“These are results from active, engaged families and individuals, many of whom are having genetic findings returned to them by a genetic counselor as a result of this research. They are people who continue to advance autism research by participating in follow up studies, through SPARK Research Match, that look at specific aspects of autism that they are passionate about and that they have a personal connection to,” says Jacob Michaelson, director of the division of computational and molecular psychiatry at the University of Iowa and SPARK investigator. “The genes are important, but it’s the thriving community behind those genes that makes this study significant to me. From that perspective, this paper marks the beginning of a new era of genetic research in autism.”
In many cases, a genetic diagnosis will not change the specific treatment plan for someone who has autism. But it can provide a relief for families that often grapple with guilt and doubt. Lynn Vigo, who enrolled in SPARK in 2016, was one of the first families in SPARK to receive a genetic result. To learn more about her experience, see this video or this story.
Analyzing DNA is a lengthy process — it takes about a year to fully process saliva samples once they are received. Families that enroll in SPARK will be notified annually if they do not have a genetic result once their sample is analyzed. As additional autism genes are uncovered, SPARK researchers will re-review gene data from families whose DNA has already been analyzed. So people who did not get a result in the first round of analysis may get one later.
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