The extensive DNA sequencing datasets associated with the SPARK cohort will enable researchers to accomplish one of the program’s key goals: identifying additional genetic variation associated with autism. Both SPARK exome and genome datasets include:

• mapped sequencing reads
• single-nucleotide polymorphism array genotyping data
• variant call files containing single-nucleotide variants and small insertions and deletions from multiple variant callers, including GATK and DeepVariant

Genotyping data from SPARK is helping to power expanded genome-wide association studies by the Psychiatric Genomics Consortium, which aims to identify common variants associated with autism with high statistical confidence. Sequence data have already been used to identify additional rare de novo mutations with high impact on autism susceptibility and have begun to provide sufficient power to identify rare mutations that are inherited from parents.

SPARK genomic data also continues to be used to explore other aspects of the etiology of autism, including the genetic origins of sex-dependent differences in diagnosis and presentation. Examples include:

• The female protective effect against autism spectrum disorder (Cell Genomics, 2022)
• Sharing parental genomes by siblings concordant or discordant for autism (Cell Genomics, 2023)
• A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk (Nature Communications, 2024)

Other findings include estimated odds ratios of autism-associated genes, and lessons learned from returning results to families.

As the datasets continue to grow, we anticipate well-powered studies attempting to associate genotypes with phenotypes, which will help researchers better understand the remarkable heterogeneity observed across the autism spectrum.

Genomic data is available for over 115,000 SPARK participants, many of whom also have phenotypic data available through SPARK :

• 106,000+ (including 44,000+ with autism) with whole exome sequencing
• 12,000+ (including 3,000+ with autism) with whole genome sequencing
• 2,000+ individuals with both

Additional information on genes implicated in autism susceptibility is available via the database SFARI Gene.

All genomic data are available to approved researchers via SFARI Base.