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Polygenic Risk Score Predicts Future Psychosis Risk

November 20, 2019

A polygenic risk score incorporating data from recent schizophrenia and bipolar genome-wide association studies predicted which high-risk patients with European ancestry went on to develop psychosis. Researchers published their findings online in The American Journal of Psychiatry.

“The 2-year risk of psychosis in persons who meet research criteria for a high-risk syndrome is about 15% to 25%; improvements in risk prediction accuracy would benefit the development and implementation of preventive interventions,” the study team wrote in their introduction.

The study included 764 people meeting research criteria for being at high risk of psychosis and 279 unaffected people.

Among participants with European ancestry, the polygenic risk score was higher in people at high risk who went on to develop psychosis, compared with those at high risk who did not develop psychosis as well as unaffected participants.

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However, among participants with non-European ancestry, the polygenic risk score difference between people at high risk who did—and did not—develop psychosis was not significant.

Researchers pointed out that because genetic risk studies mainly include Europeans, the polygenic risk score performs better in that population. They called for greater efforts to include non-Europeans in genetic risk studies as well as for improvements in polygenic risk score construction methods.

In both participants with European and non-European ancestry, the polygenic risk score was similar for high-risk participants who did not develop psychosis and for unaffected participants.

Diana O. Perkins, MD, MPH

“Previous studies reported the polygenic risk score discriminates persons with established schizophrenia from unaffected persons. Our study is the first to indicate the polygenic risk score predicts future psychosis, suggesting a polygenic risk score may facilitate the development and eventual targeting of preemptive interventions,” said study lead author Diana O. Perkins, MD, MPH, professor of psychiatry in the University of North Carolina at Chapel Hill School of Medicine.

—Jolynn Tumolo


Perkins DO, Olde Loohuis L, Barbee J, et al. Polygenic risk score contribution to psychosis prediction in a target population of persons at clinical high risk. The American Journal of Psychiatry. 2019 November 12;[Epub ahead of print].

Polygenic risk score improves psychosis risk prediction [press release]. Chapel Hill, North Carolina: University of North Carolina School of Medicine; November 11, 2019.


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