Polygenic risk score and the psychosis continuum model

Abstract

Objective: Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical characteristics and genetic risk indicating a psychosis continuum. This is the first study using polygenic risk score (PGRS) to investigate the localization of diagnostic subcategories along the entire psychosis spectrum.

Method: Based on results from the Psychiatric Genomics Consortium (PGC), we assigned a SZ and BD PGRS to each individual in our independent sample [N=570 BD spectrum cases, 452 SZ spectrum cases and 415 healthy controls (CTR)]. Potential differences in mean SZ and BD PGRS across diagnostic spectrums and subcategories were explored.

Results: SZ and BD PGRSs were significantly associated with both SZ and BD spectrums compared with CTR. For the subcategories, SZ PGRS was significantly associated with SZ, schizoaffective disorder, psychosis not otherwise specified, and BD1, while BD PGRS was significantly associated with BD1 and BD2. There were no significant differences between any of the diagnostic spectrums or subgroups for neither the SZ nor BD PGRS. Lifetime psychosis was significantly associated with SZ PGRS but not with BD PGRS.

Conclusion: These findings further support the psychosis continuum model and provide molecular polygenetic validation of the localization of diagnostic subcategories within this continuum.

Keywords: bipolar disorder; polygenic risk; psychosis spectrum; schizophrenia.