Polygenic Risk Score Contribution to Psychosis Prediction in a Target Population of Persons at Clinical High Risk

What is it about?

Schizophrenia is typically a chronic and disabling disorder affecting about 1% of adolescents and young adults. Research criteria for a clinical high-risk syndrome identify persons with a 15-25% 2-year risk of psychosis. While the 2-year risk of psychosis in persons meeting research criteria for a high-risk syndrome is about 200-fold higher than the general population risk, the prediction accuracy is still not optimal for the development and implementation of preventative interventions. Large-scale genetic studies developed a polygenetic risk score (PRS) that discriminates persons with schizophrenia from persons without schizophrenia. We discovered that the PRS improves psychosis risk prediction in persons meeting clinical high-risk criteria. Moreover, the PRS improved individualized risk assessments as part of our previously published Psychosis Risk Calculator. However, because the PRS was developed in persons of mainly European ancestry, the PRS did not perform as well in non-Europeans and it did in Europeans. Improvements in PRS construction methods and efforts to include non-Europeans in genetic risk studies are needed. With further improvements and given the relatively low cost and wide-availability of genotyping, potential applications of genetic risk scores to psychosis risk screening warrant further exploration.

Featured Image