Polygenic risk score improves psychosis risk prediction

A new study led by researchers at the University of North Carolina at Chapel Hill has found that that using a polygenic risk score (PRS) based on data from genome-wide association studies (GWAS) improves psychosis risk prediction in persons meeting clinical high-risk criteria.

“Previous studies reported the PRS discriminates persons with established schizophrenia from unaffected persons. Our study is the first to indicate the PRS predicts future psychosis suggesting a PRS may facilitate the development and eventual targeting of preemptive interventions,” said Diana O. Perkins, MD, MPH, a professor of psychiatry in the UNC School of Medicine and lead author of the study, published Nov. 12 in the American Journal of Psychiatry.

Schizophrenia is typically a chronic and disabling disorder affecting about 1 percent of adolescents and young adults. Research criteria for a clinical high-risk syndrome identify persons with a 15-25 percent 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, genome-wide association studies (GWAS) developed a polygenetic risk score (PRS) that discriminates persons with schizophrenia from persons without schizophrenia. “In this study, we discovered that the PRS improves psychosis risk prediction in persons meeting clinical high-risk criteria,” Perkins said. “Moreover, the PRS improved individualized risk assessments as part of our previously published Psychosis Risk Calculator.”

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