Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population.

Researchers studied the genetic factors behind different autism symptoms in over 6,000 autistic children. They found that different autism traits (like social communication, repetitive behaviors, and coordination) have varying levels of genetic influence. Surprisingly, genetic patterns differed between boys and girls. Repetitive behaviors showed the strongest genetic signals, suggesting they may be more genetically distinct than other autism features.

The study also found genetic links between autism traits and other conditions like ADHD and depression.

This large-scale genetic study of 6,064 autistic children examined the heritability and genetic correlations of specific autism symptom domains using clinical assessment subscales. The research found that autism subscales show variable heritability (0.04-0.24) and distinct genetic associations with other psychiatric traits. Educational attainment polygenic scores negatively correlated with most autism subscales, while ADHD and depression scores showed positive correlations. Notably, genetic influences differed by sex, with autism case-control polygenic scores showing negative correlation in females but no strong correlation in males.

The Repetitive Behavior Scale-Revised (RBS-R) demonstrated the strongest genetic signals both within autistic samples and in the general population, suggesting repetitive behaviors may have more distinct genetic architecture than other autism domains.

Findings suggest autism symptom domains have distinct genetic architectures requiring individualized assessment approaches. Sex differences in genetic patterns may inform diagnostic considerations. Strong genetic signal in repetitive behaviors supports targeted intervention development. Genetic overlap with ADHD and depression highlights importance of comprehensive psychiatric assessment in autism diagnosis and treatment planning.

Study limited to common genetic variants and may not capture rare variant contributions. Sample primarily of European ancestry may limit generalizability. Cross-sectional design prevents understanding of genetic influences on symptom development over time. Reliance on parent-report measures may introduce reporting biases.

The complexity of autism's phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is undetermined if autistic symptom domain severity underlying this heterogeneity is heritable and pleiotropic with other psychiatric and behavior traits in the same manner as autism case-control status. In N = 6064 autistic children in the SPARK cohort, we investigated the common genetic properties of twelve subscales from three clinical autism instruments measuring autistic traits: the Social Communication Questionnaire (SCQ), the Repetitive Behavior Scale-Revised (RBS-R), and the Developmental Coordination Disorder Questionnaire (DCDQ). Educational attainment polygenic scores (PGS) were significantly negatively correlated with eleven subscales, while ADHD and major depression PGS were positively correlated with ten and eight of the autism subscales, respectively.

Loneliness and neuroticism PGS were also positively correlated with many subscales. Significant PGS by sex interactions were found-surprisingly, the autism case-control PGS was negatively correlated in females and had no strong correlation in males. SNP-heritability of the DCDQ subscales ranged from 0.04 to 0.08, RBS-R subscales ranged from 0.09 to 0.24, and SCQ subscales ranged from 0 to 0.12. GWAS in SPARK followed by estimation of polygenic scores (PGS) in the typically-developing ABCD cohort (N = 5285), revealed significant associations of RBS-R subscale PGS with autism-related behavioral traits, with several subscale PGS more strongly correlated than the autism case-control PGS.

Overall, our analyses suggest that the clinical autism subscale traits show variability in SNP-heritability, PGS associations, and significant PGS by sex interactions, underscoring the heterogeneity in autistic traits at a genetic level. Furthermore, of the three instruments investigated, the RBS-R shows the greatest evidence of genetic signal in both (1) autistic samples (greater heritability) and (2) general population samples (strongest PGS associations).