LAUSR

Background Anxiety disorders are one of the most common comorbid conditions in people with bipolar disorder and are associated with unfavorable outcomes, including increased recurrence, higher rates of alcohol and substance abuse, and more frequent suicide attempts. However, the causal direction has remained unclear: Does poorer outcome lead to anxiety, or does comorbid anxiety result in poorer outcomes? Methods Here we used a Polygenic Risk Score (PGS) for anxiety to approach this question in a sample of 1754 adults with bipolar I or schizoaffective bipolar disorder previously characterized by the Diagnostic Interview for Genetic Studies (DIGS) and genotyped on Affymetrix 6.0 arrays. Anxiety PGS was calculated on the basis of results from the largest published GWAS meta-analysis of anxiety disorders (Otowa et al., 2016). Markers were LD clumped and the p-value threshold was set at 1. First we examined anxiety disorder comorbidity by creating a categorical ‘anxiety disorders’ variable comprising any DSM anxiety disorder diagnosis. Results Anxiety PGS was significantly associated with anxiety comorbidity (X2=7.756, df=1, p Discussion Taken together, these findings indicate that genetic risk for anxiety contributes to patterns of comorbidity in bipolar disorder, increasing risk for some anxiety disorders and for anorexia. Other common comorbidities and clinical features appear unrelated to genetic risk for anxiety, suggesting distinct etiologies.