SPARK (Simons Foundation Powering Autism Research for Knowledge): A US Cohort of 50,000 Families to Accelerate Autism Research
The causes of autism spectrum disorders (ASD) and the cellular mechanisms leading to ASD are not completely understood. Clinical studies to understand the brain and behavior in ASD are challenged by lack of replicability, partly due to the heterogeneity of the condition and small sample sizes. These challenges have limited progress in the development of effective treatments for this condition, and there are currently no approved medications that treat the core symptoms of ASD. Although ~100 ASD genes have been identified from studies of thousands of individuals, larger studies are required to understand the genomic architecture of ASD and identify additional monogenic, oligogenic, polygenic and environmental risk factors and to enable research studies of more homogeneously defined groups of individuals with ASD.
To accelerate clinical research in ASD, we created SPARK (Simons Foundation Powering Autism Research for Knowledge) with the goal of recruiting and retaining at least 50,000 individuals with ASD and their family members into a longitudinal, recontactable research cohort in which individual genetic causes of autism are returned to participants.
To date, we have enrolled over 30,000 individuals with ASD and over 50,000 of their family members. SPARK is recruiting approximately 1,000 additional participants with ASD each month, through a national network of 25 clinical sites and social and digital media campaigns. We have performed exome sequencing and SNP genotyping on the first 500 parent-affected offspring trios, and currently we are performing exome sequencing and genome-wide genotyping on 4,000 parent-affected offspring trios and 2,000 unaffected siblings.
Using exome sequencing of 500 ASD trios we identified de novo and inherited X- linked likely gene disrupting (LGD) variants in genes strongly associated with ASD in 4% of individuals and returned those results to participants using an innovative, centralized genetic counseling service. We have also identified de novo loss of function or damaging missense variants in 27 additional genes, including two de novo loss of function variants in BSBK2, a novel candidate gene for ASD.
We have developed a large-scale research platform that is efficient and engaging and that can be applied to other human diseases. Data from this cohort of recontactable, genetically characterized individuals with ASD are available to the research community at https://sfari.org/resources/autism-cohorts/spark. Researchers can also apply to access to this unique cohort for recruitment into research studies. SPARK represents a new era of clinical research that combines online access to participants, ability to re-contact and recruit participants for new research studies, and genomic, environmental, and longitudinal behavioral and medical information on all participants. SPARK is founded on principles that emphasize a strong partnership between participants and researchers. SPARK is committed to providing aggregate and individual research results to participants to help keep the goals of research grounded in having a meaningful impact on the lives of individuals and families with ASD. We believe that the challenges and lessons learned from SPARK will be informative to a wide range of researchers working on other conditions.