Polygenic profiles in youth with early-onset psychosis and offspring of schizophrenia or bipolar disorder patients.

The role of genetic factors shaping liability for psychosis remains unclear. Youth with first-episode, early-onset psychosis and youth at increased familial risk for psychosis show higher rates of co-occurring psychiatric diagnoses and cognitive difficulties than the general population. This study assessed polygenic scores (PGS) for psychiatric diagnoses, cognition and educational attainment in 414 youth: N = 69 cases with non-affective, early-onset psychosis (schizophrenia, schizophreniform and schizoaffective disorders), N = 62 cases with affective, early-onset psychoses (bipolar or depressive disorders with psychotic symptoms), N = 52 offspring of patients with schizophrenia, N = 94 offspring of patients with bipolar disorder, and N = 117 healthy controls. After quality control, PGS were calculated using the PRS-CS tool. Differences in PGS were examined by fitting binary logistic models. Sensitivity analyses ruled out effects of potential confounders. PGS for schizophrenia and bipolar disorder were higher in youth with non-affective, early-onset psychoses and offspring of patients with schizophrenia, and higher PGS scores for attention deficit hyperactivity disorder (ADHD) were found in youth with non-affective, early-onset psychoses and offspring of patients with bipolar disorder, relative to controls. PGS for cognition and educational attainment were lower in youth with non-affective, early-onset psychoses, compared with youth with affective, early-onset psychoses, offspring of bipolar disorder patients, and controls (all P