Featured above is SPARK’s scientific director, Pamela Feliciano, Ph.D.
Article written by Emily Singer
Autism has a strong genetic component – scientists estimate that about 80 percent of autism risk is tied to genetic changes, with the rest coming from environmental factors or a combination of genetics and environment. Many different genes are likely to contribute to the condition. Research to date suggests that 400 to 1,000 genes have a significant link to autism, and different people with autism have different genetic causes.
That diversity makes autism genetics complicated. Most risk genes are responsible for only a very small subset of autism cases, so it’s difficult to identify them. To date, scientists have found about 90 such genes. To ferret out the rest, researchers must study very large numbers of people with autism. SPARK’s goal is to fill this gap by recruiting 50,000 people with autism and their families to participate in research.
Though genetics are a central component of SPARK, the project’s purpose is far broader. SPARK scientists are building a new kind of research community, one designed to foster communication between scientists and participants. Through SPARK’s online community, people interested in research can learn about ongoing studies. Scientists can recruit participants from a large, diverse pool. Researchers who recruit from SPARK share their findings with the SPARK community, a fairly unusual occurrence in the research world.
To date, SPARK has enrolled over 35,000 individuals with autism. SPARK scientists have already uncovered some genetic results and shared them with participants. They are now gearing up for the next phase of the project. Here, Pamela Feliciano, SPARK’s scientific director, talks with science writer Emily Singer about what distinguishes SPARK from other autism research efforts and discusses some of the challenges her team has encountered along the way. For a more in-depth discussion, check out a review published in the journal Neuron in February 2018, written by Feliciano and the SPARK team.
Only 10 to 20 percent of autism-linked genes have been identified to date. Why is it so difficult to find the rest? Why do you need to study 50,000 people with autism to do so?
The field as a whole has identified the most common genes, but even those each only explain less than a percent of autism cases. The remaining genes are probably linked to autism in even smaller numbers. That means you have to sequence a lot of people to find them.
Why is it important to get a complete picture of the genetics underlying autism?
I think the biggest thing about understanding all the genes involved in autism is that we can start to make sense of the biological processes involved. For example, one idea that many researchers are studying is the possibility that an imbalance of activity in certain regions of the brain is responsible for the learning, memory, sensory and motor symptoms and seizures often present in autism. Understanding more about the genes involved in ASD can help us learn more about what is happening in cells that leads to the different features of autism. When you only know 20 percent of what’s going on, it’s harder to understand as a whole what’s happening. Once we have a clearer picture, we can start to conduct better research. We can better target the processes that are disrupted in cells.
Why is it so difficult to recruit people to participate in research studies?
Recruitment into clinical research is always challenging. We surveyed families as we were designing SPARK to try to better understand why. From what we heard, it’s hard for families to find out about ongoing studies. Time is also an issue – finding time to participate in research when therapy is pervasive in their lives. It’s hard on the kids too. Many individuals with autism have difficulty with novel environments and interacting with new people.
How does SPARK address those challenges?
What we saw in surveys of families is that people are interested in participating in research if they can. But they don’t have a means of learning about research opportunities. In our online community, we match participants with relevant opportunities. Some research studies are really easy, like an online questionnaire. Researchers are happy because we are able to quickly put them in contact with thousands of people with autism.
What has been the biggest recruitment challenge so far?
We have put a real emphasis on recruiting families – meaning a child with autism and both of his or her biological parents – when possible. Having DNA from both parents makes the genetic analysis much more powerful. But getting all members of the family to participate has been a challenge. In cases where both parents are available, we have successfully gotten both parents to participate roughly half the time. That said, we do want individuals or children and single parents to participate.
What makes SPARK different from other autism research studies?
SPARK is different than many autism research studies in that we are recruiting and having participants go through the informed consent process entirely online. We mail saliva kits to people’s homes so they can donate their biological specimens from their living rooms. SPARK’s size is certainly unique – no other autism study has this many participants. We also take a long-term approach; we continually ask people to contribute more information over time. We want to understand autism not as a single data point in someone’s life but throughout the life span. I hope that will be really valuable for the community.
How have SPARK participants helped shape the project?
We have a committee of roughly 70 members that we communicate with about a number of issues. For example, we asked for their feedback on recruitment materials and what they think would resonate with the greater autism community. That has been very helpful.
Why is it so important to foster the relationship between participants and researchers?
One thing we learned through talking to families is that when they’ve participated in research in the past, they don’t hear about how they contributed to the study. They asked, why should I participate if I don’t even know what I did to help science? Unfortunately, there’s often a long time span between when data is collected and when the results of a study are published. And scientists publish their results in journals that most people don’t read. To remedy that disconnect, we require researchers to provide feedback to participants and the whole SPARK community on what they learned. We will help researchers write up data reports that are understandable so that participants can read about how they contributed to research and what we learned from that research.
What are some challenges in giving participants results?
Returning genetic results is a labor-intensive process that requires a lot of expertise, care and attention to detail. For example, we need to make sure we are only returning genetic variants that we know are the primary genetic reason for the individual’s autism. The biggest challenge we have is being able to do it at the standard we want and to scale that up to thousands of people. We started with a pilot study of 500 people with autism and their parents and have returned a handful of results. That’s been really helpful for learning how to scale up this process going forward.
What have you learned from the pilot?
People are interested in these results, and they can be very meaningful. For some families, knowing the reason for their child’s disability brings a sense of relief. For other families, knowing the genetic variant behind their child’s autism gives them the opportunity to interact with other families with the same condition. In many cases, genetic variants are linked to specific symptoms that can be challenging. Being able to speak to others facing the same challenge can be uplifting. Sometimes there are medical implications. For people with genetic changes in SCN2A, for example, knowing the genetic variant might influence the type of epilepsy medication the individual should take. In other cases, a genetic diagnosis provides a better understanding of how to proceed with behavioral and other interventions.
What information have you shared with participants so far?
In August, we sent out our first ‘SPARK Snapshot,’ which gives some information about the people who have signed up for SPARK. We are also working on retuning individual results to anyone who filled out one of the questionnaires – the social communication questionnaire. We will tell people where they fall on different scales of communication and show them how they compare to the rest of the group enrolled in SPARK.
What are you most excited about moving forward?
I’m really looking forward to analyzing the genetic data that we have collected from thousands of autism families and identifying genetic results in – hopefully – hundreds of families. I think that returning these results serves both the families and the researchers, and I am excited for the possibilities that will come as a result of the participants’ contributions and the SPARK team’s hard work.