Use of schizophrenia and bipolar disorder polygenic risk scores to identify psychotic disorders

Br J Psychiatry. 2018 Sep;213(3):535-541. doi: 10.1192/bjp.2018.89.

Abstract

Background: There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.AimsTo investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.

Method: Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.

Results: Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.

Conclusions: Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.Declaration of interestR.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.

Keywords: Bipolar disorder; polygenic; polygenic risk scores; prediction; psychotic disorders; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australia
  • Bipolar Disorder / genetics*
  • Case-Control Studies
  • Europe
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multifactorial Inheritance
  • Polymorphism, Single Nucleotide
  • Psychotic Disorders / genetics*
  • Risk Factors
  • Schizophrenia / genetics*
  • Young Adult