Association of Polygenic Risk Scores for Schizophrenia with Psychosis-Proneness Indicators in the General Population:...

Schizotypy (ST) and psychotic-like experiences and negative symptoms (PENS) are commonly used phenotypes in high-risk and early intervention research for schizophrenia and other non-affective psychoses. However, the origin of these phenotypes in the general population is poorly understood and their association with the genetic predisposition to psychoses has not yet been proven.

The aim of this study is to answer the question of whether data on the relations of ST and PENS with polygenic risk scores for schizophrenia (SZ-PRS) support the hypothesis that these phenotypes are subclinical manifestations of genetic liability for schizophrenia.

Literature describing these relations in the general population was analyzed. The literature search was performed in the PubMed database using the following keywords in English: (("schizotyp*" OR "psychotic-like experiences" OR "psychosis proneness" OR "psychotic experiences") AND ("polygenic risk" OR "genetic liability" OR "polygenic score")); the search in eLIBRARY.RU was conducted using the Russian words for "schizotypy", "schizotypal features", "psychotic experiences", "psychotic experience", "psychotic symptoms", and "polygenic risk", covering publications from 2009 to 2024.

Of the identified records, 45 publications were found eligible. No expected positive correlations of SZ-PRS with common ST measures have been observed. For PENS, the results are inconsistent. Overall, SZ-PRS correlate more often with the PENS general factor and negative symptoms than with psychotic experiences per se.

The literature does not provide convincing evidence of the association between SZ-PRS and ST/PENS. The search for the substantive psychological meaning of polygenic vulnerability to psychosis captured by SZ-PRS should be expanded to other personality processes and traits.