Discover SPARK
What Can Autistic People Learn From Genetic Testing?
Marina Sarris
Date Published: August 8, 2024
Which autistic people are most likely to learn something from a DNA test? And what does DNA tell us about why autism is so different in each person?
The SPARK autism study, the largest of its kind, answered those questions in a new research paper. SPARK analyzed the results from sequencing the DNA of more than 21,000 of its study participants with autism, and their parents.
Researchers found variations in the DNA that caused autism in 1,861 autistic children and adults – almost 9 percent of those who had their DNA sequenced by SPARK.
People with genetic variations had some things in common. They were more likely than people without variations to have certain medical conditions, to have been diagnosed more than 20 years ago, and to be female, according to the study by researchers from SPARK and several universities.1
SPARK lets participants know if they have a genetic variation, if they choose to be told the news. “We are learning together, and it is important for participants to have the opportunity to learn about themselves in our research studies,” says Wendy Chung, M.D., Ph.D., chief of pediatrics at Boston Children’s Hospital and the lead researcher for SPARK.
Autistic people with one of the following medical conditions and features were two to five times more likely to have a genetic cause for autism1:
- cognitive delays/impairments
- motor delays
- physical differences, such as a heart defect, cleft lip, short stature, or an unusually small or large head size
- seizures or epilepsy
- misaligned eyes
- not being able to control the bowels or bladder at the typical age in childhood
Almost a third of the people with three or more of those features had a genetic variant found by SPARK.1
People diagnosed more than 20 years ago had more of these medical conditions. They were 50 percent more likely to have a genetic variant than people diagnosed more recently.1 This difference may have been influenced by changes in autism awareness and diagnostic guidelines for autism that took place over time, says SPARK scientist Jessica Wright, Ph.D., the study’s lead author.
More autistic people who do not have intellectual disability are being diagnosed with autism today than several decades ago.
Getting a Fuller Picture of Rare Genetic Conditions
Some people who received a genetic diagnosis from SPARK – about 4 percent – did not have seizures, cognitive impairment, or any of the other conditions that occurred more often in people with a genetic variation. That’s important because it expands what we know about how a genetic condition can affect people.
SPARK is learning new information about genetic variants because of how it recruits participants for DNA sequencing. Outside of SPARK, most people who get genetic testing must see a medical specialist who decides whether to order the test. Their insurance companies decide whether to pay for testing.
By contrast, more than half of SPARK participants found out about the study on social media or online. They sent in their saliva sample from home for DNA analysis, at no cost to them. SPARK analyzes the DNA of every participant who provides a sample, rather than deciding who is more likely to have a genetic condition, as doctors or insurance companies would do.
The Influence of Sex Assigned at Birth
Autism is diagnosed much more often in males than females, but SPARK, like other studies, has found that autistic girls and women are more likely to have a genetic condition that triggered their autism.1,2
Scientists have long suspected that girls are somehow protected from developing autism. Many people with autism may have minor genetic changes that have not been discovered by researchers so far. According to one theory, girls with these minor changes are less likely to develop autism than boys.
But when girls do have autism, it’s more likely due to a major change in their DNA, like the variations uncovered by SPARK’s testing, called exome sequencing.
Many Different Genetic Paths to Autism
Just as autism affects people differently, the genes found to contribute to autism vary widely, according to this SPARK study. Autism differs from other genetic conditions that may involve a change to a single gene or chromosome. Researchers found more than 400 changes to either different genes or parts of chromosomes in autistic participants in SPARK.1
More than 40 percent of these genetic variations affected only one person. The most common finding, a deletion in a part of chromosome 16, affected less than 1 percent of SPARK participants on the spectrum.
Unlike some studies, SPARK will tell participants if they have a genetic variant related to autism. Participants decide whether they want to know their results, and most do. They can choose to have the result sent to their doctor, or they can meet with a genetic counselor for free.
The Personal Impact of a DNA Test
The King family, of Washington state, joined SPARK to contribute to research into autism, which affects their son Travis. “We knew we wanted to be part of an autism study, but we didn’t know if we’d learn anything and we waited two years for an answer,” says Threasa King, Travis’s mother.
SPARK notified the Kings that it had genetic news for Travis several years ago. “When we did get our answer, we were surprised and excited because then we knew what our next steps to help our son could be,” Threasa King says. “And to me, this is a way for him to help people that are like him.”
Travis King, now 20, has a rare variation to a gene called CUL3. Most variations found by SPARK were not inherited from parents, and that was also true for King.
Besides autism, CUL3 is linked to high blood pressure. With this information, King’s doctor changed a medicine he was taking that was causing his blood pressure to jump up and down.
Other SPARK participants have reported similar benefits to receiving a genetic result, according to two recent studies. Like the Kings, some learned that a variant carried a risk for other medical conditions. Other participants had variants so rare that little medical information was available. Some parents said that learning about their child’s genetic condition helped them, and others, understand their child’s needs better.3,4
No similar studies have been published about the effect of a genetic diagnosis on independent autistic adults. In interviews, three autistic adults who received a genetic diagnosis from SPARK said that they were glad to contribute to autism research or learn something about themselves.
“It’s hard to express just how meaningful hearing about these genetic changes can be for people who have wondered about themselves, or their family members, for years, even if it doesn’t immediately change how they approach their medical care,” says Wright, the study’s lead author. “For autistic people it can be another step toward understanding themselves. For families, it can release nagging feelings of misplaced guilt, or feel like the end of a massive diagnostic odyssey. We are immensely proud that we’ve tackled the challenge of communicating findings to participants from such a massive study.”
Does a Negative DNA Test Mean Your Autism Isn’t Genetic?
SPARK will reanalyze the DNA of participants for whom it did not find any genetic changes. That’s because new genetic variants are still being uncovered by researchers. Participants may have a genetic change that has not been linked to autism yet.
Researchers began identifying variants that have a major effect on autism first. These variants were easier to find because they were more likely to cause autism or intellectual disability than other variants.
But researchers hope with time to uncover more variants, including those that do not cause autism on their own, and are more likely to be inherited.
“We hope people with autism and their families can use this information to understand more about themselves and unlock their full potential,” Chung says.
To learn more, watch Wright’s webinar on “What SPARK is Learning from Returning Genetic Results to Participants with Autism.”
Interested in joining SPARK? Here’s what you should know.
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