Clinical autism subscales have common genetic liability that is heritable, pleiotropic, and generalizable to the general population
The complexity of autism's phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is unclear whether clinical autism instruments such as the Social Communication Questionnaire (SCQ), Repetitive Behaviors Scale-Revised (RBS-R), and Developmental Coordination Disorder Questionnaire (DCDQ) are more genetically informative than case-control. We employed the SPARK autism cohort (N = 6,449) to illuminate the genetic etiology of these twelve
... es. In comparison to the heritability of autism case-control at 0.12, the RBS-R subscales were increased, ranging from 0.18 to 0.30 (all p < 0.05). Heritability of the DCDQ subscales ranged from 0.07 to 0.09 and the SCQ subscales from 0 to 0.09 (all p > 0.05). We also found evidence for genetic correlations among the RBS-R, SCQ, and DCDQ. GWAS followed by projection of polygenic scores (PGS) into ABCD revealed significant associations with CBCL social and thought problems, while the autism case-control PGS did not significantly associate. In phenotypic correlation analyses, the autism case-control PGS did not predict the subscales in SPARK, and sex-stratified correlations showed no effect in males and a surprising negative effect in females. Notably, other PGS did predict the subscales, with the strongest being educational attainment negatively correlated, while ADHD and major depression were positively correlated. Overall, our analyses suggest that clinical subscales are more genetically powerful than case-control, and that of the three instruments investigated, the RBS-R shows the greatest evidence of common genetic signal in both autistic and general population samples.