We modeled the genome-wide joint architecture of the eight neuropsychiatric disorders using an exploratory factor analysis (EFA) (Gorsuch, 1988), followed by genomic structural equation modeling (SEM) (Grotzinger et al., 2019) (Online Methods; Fig. 1c). EFA identified three correlated factors, which together explained 51% of the genetic variation in the eight neuropsychiatric disorders (Table S2.2). The first factor consisted primarily of disorders characterized by compulsive/perfectionistic behaviors, specifically AN, OCD, and, more weakly, TS. The second factor was characterized by mood and psychotic disorders (MD, BIP, and SCZ), and the third factor by three early-onset neurodevelopmental disorders (ASD, ADHD, TS) as well as MD. Similar to our EFA results, hierarchical clustering analyses also identified three sub-groups among the eight disorders (Data S1.1). Based on extensive follow-up analyses, this genetic correlational structure does not appear to be biased by sample overlap or sample size differences among the eight disorders (Data S1.2–1.4).
