Schizophrenia and Bipolar Polygenic Risk Scores in Relation to Intracranial Volume

Schizophrenia and bipolar disorder are neurodevelopmental disorders with overlapping symptoms and a shared genetic background. Deviations in intracranial volume (ICV)-a marker for neurodevelopment-differ between schizophrenia and bipolar disorder. Here, we investigated whether genetic risk for schizophrenia and bipolar disorder is related to ICV in the general population by using the UK Biobank data (n = 20,196). Polygenic risk scores for schizophrenia (SZ-PRS) and bipolar disorder (BD-PRS) were computed for 12 genome wide association study P-value thresholds (P-T) for each individual and correlations with ICV were investigated. Partial correlations were performed at each P-T to investigate whether disease specific genetic risk variants for schizophrenia and bipolar disorder show different relationships with ICV. ICV showed a negative correlation with SZ-PRS at P-T >= 0.005 (r < -0.02, p < 0.005). ICV was not associated with BD-PRS; however, a positive correlation between BD-PRS and ICV at P-T = 0.2 and P-T = 0.4 (r = +0.02, p < 0.005) appeared when the genetic overlap between schizophrenia and bipolar disorder was accounted for. Despite small effect sizes, a higher load of schizophrenia risk genes is associated with a smaller ICV in the general population, while risk genes specific for bipolar disorder are correlated with a larger ICV. These findings suggest that schizophrenia and bipolar disorder risk genes, when accounting for the genetic overlap between both disorders, have opposite effects on early brain development.