Association of Schizophrenia-Related Polygenic-Risk Score Across Bipolar Disorder Subtypes

scientist holding DNA autoradiogram
scientist holding DNA autoradiogram
A schizophrenia-related polygenic-risk score association gradient was identified across bipolar disorder phenotypes.

In a recent study published in JAMA Psychiatry, a schizophrenia-related polygenic-risk score association gradient was identified across bipolar disorder phenotypes, with strong associations between polygenic-risk scores and schizoaffective bipolar disorder and bipolar disorder with psychotic features.

In this case-control study, researchers evaluated the association between schizophrenia-related polygenic-risk scores with subtypes of bipolar disorder, lifetime occurrence of psychosis, and lifetime mood-incongruent psychotic features. They included 4436 participants with bipolar disorder and genotypic data from the Bipolar Disorder Research Network (67% female; mean [SD] age 46 [12]). Comparators included genotypic data from 4976 cases of schizophrenia and 9012 controls from the Type 1 Diabetes Genetics Consortium study and the Generation Scotland study. The calculated schizophrenia-related polygenic-risk scores were based on the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia.

An exposure-response gradient across clinical bipolar disorder phenotypes was reported, with the strongest polygenic-risk score association for schizophrenia (risk ratio [RR] 1.94; 95% CI, 1.86-2.01). Schizoaffective bipolar disorder had the next strongest association (RR 1.37; 95% CI, 1.22-1.54), followed by bipolar I disorder (RR 1.30; 95% CI, 1.24-1.36) and bipolar II disorder (RR 1.04; 95% CI, 0.97-1.11).

Prominent mood-incongruent psychotic features were strongly associated with polygenic-risk scores (RR 1.46; 95% CI, 1.36-1.57), followed by mood-congruent psychosis (RR 1.24; 95% CI, 1.17-1.33), and bipolar disorder with no history of psychotic symptoms (RR 1.09; 95% CI, 1.04-1.15).

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The study investigators concluded that the results “show a gradient of polygenic liability across [schizophrenia] and [bipolar disorder], indexed by the occurrence and level of mood incongruence of positive and disorganized psychotic symptoms…further research could potentially aid in defining patient stratifiers with improved biological precision and validity, moving us tentatively toward precision medicine in psychiatry.”


Allardyce H, Leonenko G, Hamshere M, et al. Association between schizophrenia-related polygenic liability and the occurrence and level of mood-incongruent psychotic symptoms in bipolar disorder [published online November 22, 2017]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.3485