Genetic Risk of Psychosis in Relation to Cannabis Use: Findings from Polygenic Risk Score Approaches

Abstract

A psychotic disorder is a multifactorial phenomenon in which not only environmental influences but also genetic factors play an important role. Evidence indicates that psychotic disorders are characterized by a complex mode of inheritance with high polygenicity, in which a large number of common genetic variants with small effects are relevant. One way to measure this polygenic risk is the calculation of polygenic risk scores (PRS). These reflect the complex multifactorial interaction of coding and regulatory DNA variants in the development of mental illness. It is known that the use of cannabis in patients with schizophrenia (SCZ) is much higher than in the general population. Although an exact clinical prognosis based on PRS is not possible at the present, the results found by PRS investigations so far are quite promising. Initial results suggest that people with SCZ and an increased polygenic risk of schizophrenia are more likely to use cannabis. According to these results, the connection between mental illnesses and cannabis use could therefore not simply be seen as an environmental risk, but rather explained as a gene-environment correlation.