Abstract

The breadth of the diagnostic criteria for autism allows for different individuals to access important clinical, educational, and social support services. However, the substantial heterogeneity in autism is a challenge for investigating the aetiology and translating research findings to support autistic people. Using data from up to 12,893 autistic individuals, we investigate genetic differences between autistic individuals based on core and associate autism features, co-occurring developmental disabilities including intellectual disability, and sex. We demonstrate that the core and associate phenotypic profile in autism is genetically complex, involving both common and rare variants. We identify widespread differences in common and rare variants between autistic individuals based on sex, intellectual disability, and other co-occurring developmental disabilities. Furthermore, we identify differences in developmental outcomes and sex-bias in genes associated with severe developmental disorders versus other constrained genes. Altogether, our analyses demonstrate substantial phenotypic and genetic differences in subgroups of autistic individuals and highlight avenues to investigate heterogeneity in autism.