Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder

The Mood Disorder Questionnaire (MDQ) is a common screening tool for bipolar disorder that assesses manic symptoms. Its utility for genetic studies of mania or bipolar traits has not been fully examined. We psychometrically compared the MDQ to self-reported bipolar disorder in participants from the United Kingdom National Institute of Health and Care Research Mental Health BioResource. We conducted genome-wide association studies of manic symptom quantitative traits and symptom subgroups, derived from the MDQ items (N = 11,568-19,859). We calculated genetic correlations with bipolar disorder and other psychiatric and behavioral traits. The MDQ screener showed low positive predictive value (0.29) for self-reported bipolar disorder. Neither concurrent nor lifetime manic symptoms were genetically correlated with bipolar disorder. Lifetime manic symptoms had a highest genetic correlation (r_g  = 1.0) with posttraumatic stress disorder although this was not confirmed by within-cohort phenotypic correlations (r_p  = 0.41). Other significant genetic correlations included attention deficit hyperactivity disorder (r_g  = 0.69), insomnia (r_g  = 0.55), and major depressive disorder (r_g  = 0.42). Our study adds to existing literature questioning the MDQ's validity and suggests it may capture symptoms of general distress or psychopathology, rather than hypomania/mania specifically, in at-risk populations.