Characterization of sex differences in autism by polygenic clustering

Previous research has found large differences in ASD sex ratios by age of diagnosis. Our striking preliminary data define genetic clusters of ASD probands that are strongly correlated with both diagnosis age and sex ratio in the Simons Foundation SPARK cohort, and show differing polygenic risk for other psychiatric disorders. In order to replicate these findings in independent cohorts, this project will use ASD-ascertained research data (SPARK/MSSNG/SSC), EHR-linked medical data (BioVU), and prospectively collected population data (MoBa). If this yields the same observations in these cohorts, the team plans to extend its understanding of the genetic clusters, characterize individuals in each cluster and by sex based on autism traits, developmental trajectories, and medical/physiological conditions, and define the genetic and familial basis of the cluster distinction and its intersection with sex differences. This project aims to integrate its findings into an understanding of the nature of the observed genetic clusters with respect to the intersection between sex differences, age of diagnosis, and other psychiatric conditions.