NEW YORK (GenomeWeb) – The Simons Foundation Autism Research Initiative (SFARI) last week launched a 50,000-volunteer study, called SPARK, in the hopes of mapping out how genes, other biological mechanisms, and the environment interact to cause the spectrum of symptoms seen in patients.
It is well recognized now that autism is a heterogeneous condition, with a strong genetic component and a variety of phenotypes. Researchers have identified around 50 genes associated with autism, mostly commonly inherited variations conferring small increases in risk and rarer de novo and inherited genetic changes imparting greater risk. Experts estimate there could be well over 300 additional genes implicated in the condition.
Beyond genetics, studies have also explored the association between autism and metabolic factors, viral infections, and chemicals. "When you start powering this and start thinking of the sample size that you need to understand etiologies, 50,000 is a reasonable number to really get into it and understand the genetic basis," said Wendy Chung, director of clinical research at the Simons Foundation and director of the clinical genetics program at Columbia University.
According to SFARI, SPARK is the "largest autism study ever undertaken in the US." Researchers plan to enroll 50,000 individuals with autism, and additionally, their families. Last year, the Simons Foundation awarded a $4.6 million grant to Kaiser Permanente to create a database of 5,000 family trios, containing their de-identified genetic, medical, and environmental information for researchers to study autism.
The Simons Foundation is among the supporters of the iHART project, where researchers from Stanford University and other institutions are developing an open data repository — including phenotypic, proteomic, metabolomic, genomic, and a variety of other information — on 10,000 individuals with autism and their families. The project will allow users to employ tools to run queries on this data.
In another project, called MSSNG, Autism Speaks and the Hospital for Sick Children's Center for Applied Genomics is conducting whole-genome sequencing of 10,000 autism patients and family members, and making the genomic, phenotypic, and clinical data freely available to researchers on the Google Cloud.
Within SPARK, all participants who consent to be genetically tested and mail in saliva samples will be genotyped and have their exomes sequenced. There will be one central laboratory analyzing the DNA, but SFARI hasn't yet decided which lab that will be.
Researchers hope to confirm the genetic variants identified in other studies and make significant headway in discovering new ones. Compared to other mental health conditions, such as schizophrenia, "we have been underpowered as a community to be able to assess inherited variants," Chung said. She hopes SPARK will be a landmark study in terms of the diversity of participants it involves and breadth of data it collects, not just on genetics but also environmental factors, such as prenatal and early life developmental exposures.
SFARI wants to recruit autism patients and their families from around the country, spanning different ethnic and age groups. However, the traditional way of doing research — where patients come to a single study site, donate a blood sample, and engage in lengthy evaluations — didn't make much sense since SPARK investigators are expecting to enroll such a large cohort in a relatively short time.
After talking with people in the autism community, Chung and her colleagues felt it was important to make it really easy to join SPARK. Autism "takes a toll on a family," Chung recognized. "They're very burdened in terms of what they have to deal with and these evaluations take time."
SFARI designed the study so patients and their families can participate from their homes, spending between 20 to 30 minutes to register and answer high level questions through a smartphone, tablet, or computer. In addition to joining online, participants can also enroll through 21 sites at medical schools and research institutions around the country.
Genomics researchers are starting to employ online and mobile technology-facilitated enrollment as a way to reach study subjects who otherwise wouldn't participate and remove some of the barriers that have kept clinical trial participation historically low in the US. Approximately, 20 percent of clinical trials fail to recruit any volunteers, and in cancer, researchers often lament that only 3 percent of patients join studies.
Earlier this month, 23andMe announced the availability of a new module within Apple's open source ResearchKit software that would allow 23andMe customers to upload their genetic data and give consent to apply that information for studies. So far, the Asthma Health app at Mount Sinai and the MyHeart Counts app at Stanford Medicine will implement the 23andMe module.
23andMe is also getting ready to launch a service that will allow researchers to easily incorporate genetic information into studies and return results from its commercial genotyping service to volunteers. As part of this service, investigators can have 23andMe's saliva kits mailed to the participants' home for sample collection. "Someone can participate in research sitting on their couch anywhere in the country," Ruby Gadelrab, 23andMe's VP of commercial marketing, recently told GenomeWeb.
Since children with autism often don't want to be stuck with a needle to give a blood sample, SPARK participants will receive a saliva collection kit in the mail for donating a sample for genomic analysis. In addition to the individual with autism, researchers also hope to test parents and siblings in order to identify de novo and inherited mutations.
Before Chung and her colleagues launched SPARK, they tested out its feasibility in a smaller pilot. There were 2,000 participants in this phase, and Baylor College of Medicine is still in the process of collecting samples and performing exome sequencing on them.
In order to partake in the study, volunteers must reside in the US, have a professional diagnosis of autism, and agree to be recontacted about other studies. The design of the study will enable researchers to do much more than publish their findings in a peer-reviewed journal, Chung noted. Investigators will be able to keep in contact with participants in order to provide individual level results and perform in depth studies on rare genetic or other factors.
Researchers involved in other studies will also have a way to identify potential participants within the SPARK cohort. "For researchers, SPARK provides a large, well-characterized cohort of genetic, medical, and behavioral data, and will result in cost savings for researchers by reducing start-up costs for individual studies," SFARI said in a statement.
"We hope this will be a different style of research, where we are really changing the underlying principles," Chung said. "We want this to be a community, reciprocal interchange, where we're learning together, and we're quickly translating this information and giving it back, much faster than studies have done heretofore."