Schizophrenia-associated polygenic liability and structural genomic risk demonstrate broadly distributed neuropsychiatric associations in the All of Us Research Program

The study analyzed 71,992 participants from the All of Us Research Program, including 2,115 carriers of structural variants in genes associated with neurodevelopmental disorders. Researchers examined how polygenic schizophrenia risk and structural genomic changes relate to various psychiatric and neurodevelopmental disorders. Carriers of structural variants had higher risk of schizophrenia diagnosis (1.49 times higher) and each increase in polygenic risk score was associated with higher risk of psychotic symptoms (1.07 times per unit). The prevalence of psychotic symptoms increased from 5.4% in the lowest risk group to 6.7% in the highest risk group. Both forms of genetic liability showed associations extending beyond schizophrenia diagnosis to other neuropsychiatric disorders. The research found limited evidence of interaction between polygenic risk and structural variants.