The past decade has witnessed the confirmation of the idea that autism is frequently caused by spontaneous gene mutations — and that the genes responsible may be discovered by sequencing large numbers of families affected by the condition. Sequencing studies of cohorts such as the Simons Simplex Collection — a repository of genetic, biological and behavioral data from more than 2,600 families consisting of one child with autism and unaffected parents and siblings — have already established more than 70 high-confidence autism risk genes and several hundred more candidate genes.
But between 500 and 1,000 genes are believed to underlie the condition, and researchers have long known that uncovering them all will require a much larger number of families. To tackle this challenge, in April 2016 SFARI announced the launch of SPARK (Simons Foundation Powering Autism Research for Knowledge), an initiative that will collect behavioral profiles and DNA samples from 50,000 families affected by autism over the next four years. Already, the initiative has enrolled more than 20,000 individuals with autism.
Having genetic data from 50,000 families should bring the autism research community closer to ‘saturation’ in terms of cataloging the genetic causes of autism, says Wendy Chung, the initiative’s principal investigator and SFARI’s director of clinical research. “At SFARI, one of our basic beliefs is that a true understanding of the genetic causes of autism will anchor us in terms of understanding the biological mechanisms,” Chung says. “So 50,000 families became the goal for SPARK.”
SPARK’s mission is much broader than creating a catalog of autism genes. The initiative also aspires to foster a mutually beneficial community of researchers and families. All families who join SPARK agree to be notified of opportunities to participate in future studies, so SPARK could help overcome one of the biggest hurdles individual autism researchers face: recruiting enough participants who are eligible for their studies. The initiative’s leaders hope that this relationship will lay the foundation for autism research for years to come.
“A researcher contacted me recently, for example, asking me how many verbal children between 6 and 10 are enrolled in SPARK,” says Pamela Feliciano, SPARK’s scientific director. “SPARK will make this data available and searchable online so researchers can see how many people meet the criteria for their studies.”
As researchers carry out studies on the SPARK cohort, the data they add to the collection will make SPARK increasingly valuable, Chung says. “This is a long-term investment to create an infrastructure for the autism research community for a very long time.”
Because of its heterogeneity — both genetic and phenotypic — autism has come to be seen not as a single condition, but as many related conditions. “The challenges are not the same for everyone on the spectrum, and the supports and treatments won’t be the same either,” Chung says.
Families who enroll in SPARK have the option of being informed if the initiative discovers a mutation that accounts for the individual’s autism. “We believe that we will be able to return results to 5 to 10 percent of families in the beginning,” Feliciano says. “As our knowledge grows, that number will increase.”
As SPARK enrolls more and more families and discovers new autism genes, it will identify individuals with any one of the known autism risk genes who can be asked to participate in further research. Doing so will allow researchers to study particular genetic subtypes of autism and, down the road, potentially create customized treatments for autism. It will also allow families with shared genetic causes to form communities, potentially through the Simons Variation in Individuals Project, which currently provides a forum in which families with any 1 of about 50 different genetic variants can come together.
SPARK’s creators want the initiative to be rewarding for the families who participate, so in addition to returning genetic results to some families, the initiative also offers webinars on topics related to autism, and provides individualized findings from the behavioral questionnaires for each child, which families can bring to their health care providers to help inform the child’s care. “As we’re learning, we want to make sure that we’re not just keeping all these data for researchers, but that the families are learning about themselves at the same time,” Chung says. SPARK’s webinars in its first nine months of operations have attracted about 1,800 attendees.
The families will also tell researchers, Chung hopes, about the issues that are most important to individuals and families with autism. “We view SPARK not just as a research cohort, but as a partnership with families,” she says.
To enable the initiative to scale to 50,000 families, SPARK’s creators have tried to make it easy to join. Individuals can register online and then fill out a questionnaire and collect family members’ saliva samples at home, which are returned to SPARK by mail. To recruit families, the initiative has given grants to 24 clinical sites across the country that host major autism centers. SPARK’s leaders have also reached out to autism community and advocacy groups, which are helping to get the word out. SPARK’s investigators plan to do genomic analyses on participants’ saliva samples. These analyses will include both sequencing, which will help identify rare genes that cause autism, and genotyping, which will highlight more common genetic variants that don’t necessarily cause autism individually, but that might be responsible for the condition when combined with the right mix of other genetic variants or environmental triggers. “We hope that this approach will cover all genetic angles,” Chung says.
So far, the initiative has sequenced about 500 families. It plans to release these genetic data for scientists’ use in 2017, Feliciano says. “SPARK will make data available to eligible scientists as soon as it is ready.”
The initiative is generating an enthusiastic response from families affected by autism, many of whom have shared their stories on SPARK’s website and on social media, posting pictures and commentary under the hashtag #WeAreSpark. “That has been incredibly gratifying,” Chung says. “We’re all starting to come together.”