Polygenic risk scores could aid in risk reduction advice and early interventions in psychosis, according to research published in The British Journal of Psychiatry.
While polygenic risk scores are not yet ready for clinical use, researchers found that patients with psychosis had significant increases in schizophrenia and bipolar polygenic risk scores. There is a shared genetic susceptibility between schizophrenia and bipolar disorder and while each individual variant has a low predictive power, a polygenic risk score (PRS) is a significantly stronger disease predictor.
In order to determine whether schizophrenia and bipolar PRS can differentiate people with broadly defined psychosis and unaffected relatives from control subjects, researchers used the Psychiatric Genomics Consortium data to calculate schizophrenia and bipolar disorder PRS for 1168 people with psychosis, 552 unaffected relatives, and 1472 controls.
While the accuracy of predictive models was modest, patients with broadly-defined psychosis had high increases in schizophrenia and bipolar PRSs. The schizophrenia and bipolar disorder PRSs accounted for 9% and 2%, respectively, of the variance in psychosis risk. Relatives also had increases in PRSs, although at a reduced degree.
The performance of PRSs is expected to improve as larger samples are collected internationally and more rare genetic variants are being identified. Socioenvironmental factors, gene-gene, and gene-environmental interactions may also be incorporated in future PRSs. Researchers concluded that “PRSs constitute a powerful research tool, that combined with large epidemiological studies of environmental risks are advancing our understanding of the etiology of psychotic disorders.” They have the potential to reduce environmental risk and facilitate access to early treatment as they become increasingly precise.
Disclosures: Robin M. Murray has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka, and Sunovian.
Calafato MS, Thygesen JH, Ranlund S, et al. Use of schizophrenia and bipolar disorder polygenic risk scores to identify psychotic disorders. Br J Psychiatry. 2018;213(3):535-541.