Polygenic risk scores tied to episode polarity in bipolar disorder

Polygenic risk scores (PRS) for bipolar disorder, major depression, and schizophrenia are predictive of episode polarity and psychotic symptoms in a similar manner among individuals with bipolar disorder, suggests a recent study.

Specifically, PRS for bipolar disorder positively correlated with any manic episodes (odds ratio [OR], 1.23, 95 percent confidence interval [CI], 1.09‒1.38).

PRS for depression, on the other hand, showed a positive relationship with any depressive (OR, 1.11, 95 percent CI, 1.01‒1.23) and mixed (OR, 1.15, 95 percent CI, 1.03‒1.28) episodes and a negative interaction with any manic episodes (OR, 0.76, 96 percent CI, 0.69‒0.84).

PRS for schizophrenia also positively correlated with any manic episodes (OR, 1.13, 95 percent CI, 1.01‒1.27), but only when psychotic symptoms were existing (OR for psychotic mania, 1.27, 95 percent CI, 1.05‒1.54; OR for nonpsychotic mania, 1.06, 95 percent CI, 0.93‒1.20).

Additionally, similar patterns were observed for first-episode polarity and for the number of episodes within each pole.

The study included 2,705 individuals who were diagnosed with bipolar disorder at Danish psychiatric hospitals between January 1995 and March 2017. The authors obtained DNA from dried blood spots collected at birth as part of routine screening.

A meta-PRS method that combined internally and externally trained components was used to generate PRSs for bipolar disorder, major depression, and schizophrenia.

Finally, the authors explored the associations between PRS and polarity at first episode, polarity at any episode, and number of episodes with a given polarity for each disorder-specific PRS using logistic and negative binomial regression, adjusted for the other two PRSs, age, sex, genotype platform, and five ancestral principal components.