Return of genetic research results in 21,532 individuals with autism.

Purpose: The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK (SPARKforAutism.org): a large recontactable cohort of people with autism in the United States. We also describe the process to return these clinically confirmed genetic findings.

The Genotype and Phenotypes in Families (GPF) platform manages the large and complex data at SFARI.

The exploration of genotypic variants impacting phenotypes is a cornerstone in genetics research. The emergence of vast collections containing deeply genotyped and phenotyped families has made it possible to pursue the search for variants associated with complex diseases. However, managing these large-scale datasets requires specialized computational tools tailored to organize and analyze the extensive data.

Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes.

To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (P < 2.5 × 10), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2).

Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes.

Autism spectrum disorder (ASD) is a genetically heterogeneous condition, caused by a combination of rare de novo and inherited variants as well as common variants in at least several hundred genes. However, significantly larger sample sizes are needed to identify the complete set of genetic risk factors. We conducted a pilot study for SPARK (SPARKForAutism.