Genetic Evidence For Psychiatric Disorders As The Extreme End of A Continuum of Population Traits

Abstract Psychiatric disorders are highly heritable and polygenic, with numerous common genetic risk variants implicated. Twin and molecular genetic studies suggest that some clinically diagnosed psychiatric disorders (e.g. attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD)) share genetic risk with quantitative variation in milder traits of the same disorder throughout the general population. We utilized the latest emerging results from genome-wide association studies (GWAS) of 8 psychiatric disorders to test for genetic overlap across each of these clinically diagnosed psychiatric disorders and related continuously distributed population traits. GWAS summary statistics for 8 psychiatric phenotypes were used to derive polygenic risk scores (PRS) in a Swedish population of twins (N=13,472 individuals) with data available at ages 9, 12, 15 and 18 years (Child & Adolescent Twin Study in Sweden). We tested for association between PRS for a given psychiatric disorder with traits related to the same disorder, assessed using parent- and self-report questionnaires. After applying a false discovery rate to account for multiple testing, the results showed support for a significant association between PRS for psychiatric disorder with corresponding childhood population traits for the following phenotypes: ADHD (beta(SE)=0.278(0.0295), p=6.8E-20), ASD (beta(SE)=0.0366(0.0137), p=0.019), tic disorders (beta(SE)=0.0126(0.00387), p=0.0063), depression (beta(SE)=0.273(0.105), p=0.021), anxiety disorders (beta(SE)=0.202(0.0795), p=0.023), Obsessive Compulsive Disorder(OCD; beta(SE)=0.122(0.0447), p=0.019) and schizophrenia (beta(SE)=0.0561(0.0208), p=0.019). No association was seen for bipolar disorder PRS and adolescent mania symptoms. Results persisted after excluding individuals with relevant ICD diagnoses from analyses. This study provides evidence for shared genetic risks across clinical disorder and corresponding population traits assessed in childhood, for a range of psychiatric conditions. The results support the hypothesis that psychiatric disorders are the extreme ends of continuous distributions of population traits.