High-impact rare genetic variants in severe schizophrenia

Abstract

Significance In this study, we found that selecting individuals with extremely severe forms of schizophrenia led to a significantly improved ability to detect disease-associated rare variants. The high prevalence of rare variant risk factors in individuals with severe, extremely treatment-resistant schizophrenia suggests future clinical opportunities for risk prediction, prognostic stratification, and genetic counseling. These findings have implications for the design of future genetic studies in schizophrenia and highlight a strategy to reduce phenotypic heterogeneity and improve gene discovery efforts in other neuropsychiatric disorders.