Polygenic Risk and Episode Polarity Among Individuals With Bipolar Disorder

The authors investigated associations between polygenic liabilities for bipolar disorder, major depression, and schizophrenia and episode polarity among individuals with bipolar disorder.

The sample consisted of 2,705 individuals diagnosed with bipolar disorder at Danish psychiatric hospitals between January 1995 and March 2017. DNA was obtained from dried blood spots collected at birth as part of routine screening. Polygenic risk scores (PRSs) for bipolar disorder, major depression, and schizophrenia were generated using a meta-PRS method combining internally and externally trained components. Associations between PRS and polarity at first episode, polarity at any episode, and number of episodes with a given polarity were evaluated for each disorder-specific PRS using logistic and negative binominal regressions adjusted for the other two PRSs, age, sex, genotype platform, and five ancestral principal components.

PRS for bipolar disorder was positively associated with any manic episodes (odds ratio=1.23, 95% CI=1.09-1.38). PRS for depression was positively associated with any depressive (odds ratio=1.11, 95% CI=1.01-1.23) and mixed (odds ratio=1.15, 95% CI=1.03-1.28) episodes and negatively associated with any manic episodes (odds ratio=0.76, 95% CI=0.69-0.84). PRS for schizophrenia was positively associated with any manic episodes (odds ratio=1.13, 95% CI=1.01-1.27), but only when psychotic symptoms were present (odds ratio for psychotic mania: 1.27, 95% CI=1.05-1.54; odds ratio for nonpsychotic mania: 1.06, 95% CI=0.93-1.20). These patterns were similar for first-episode polarity and for the number of episodes within each pole.

PRSs for bipolar disorder, major depression, and schizophrenia are associated with episode polarity and psychotic symptoms in a congruent manner among individuals with bipolar disorder.