The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.

BackgroundDifficulties with aspects of social interaction, including empathy, comprise a core symptom of autism spectrum conditions (autism). Sympathy is a specific form of empathy and involves both cognitive and affective empathy. Data are presented from a new task of self-reported sympathy and personal distress.MethodsParticipants with autism (93 males; 161 females) and controls (40 males, 93 females) took part in an online survey via the Autism Research Centre or Cambridge Psychology websites. Participants completed a task where they were asked to rate photographic images that were either of distressing, neutral or happy scenes, according to the amount of sympathy they had for the individual in the photo and the degree of personal distress they felt. All participants also completed the Empathy Quotient (EQ).ResultsSignificant differences were found between the autism and control groups for both self-reported sympathy and personal distress, with participants with autism giving lower ratings than controls. Control females scored significantly higher than control males in both sympathy and distress. Sympathy and distress ratings in the autism group did not differ significantly by sex. EQ showed positive correlations with sympathy and distress scores.ConclusionsUsing a new measure of self-reported sympathy, we found that both males and females with autism gave lower ratings of sympathy when viewing people in distressing scenarios, compared to controls.

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