Strong Genetic Overlaps Between Dimensional and Categorical Models of Bipolar Disorders in a Family Sample

Objective: To determine the heritability and genetic relationships between dimensional and categorical models of bipolar disorder (BD). Methods: The Mood Disorder Questionnaire (MDQ) assesses lifetime history of cardinal manic symptoms and associated impairment. MDQ were collected from participants in the Amish-Mennonite Bipolar Genetics (AMBiGen) study, which enrolls individuals with BD and their relatives from Amish and Mennonite communities in North and South America. Principal Component Analysis (PCA) was performed to analyze the dimensions of the MDQ in 726 participants, 212 of whom were assigned a categorical major mood disorder diagnosis by structured psychiatric interview. SOLAR-ECLIPSE (v9.0.0) was used to perform heritability and genetic correlation analyses between MDQ-derived measures and categorical diagnoses among 432 genotyped participants. Results: As expected, MDQ scores were significantly higher among individuals diagnosed with Bipolar Spectrum Disorders (BSD). PCA suggested a three-component model for the MDQ, consistent with the literature. Heritability of the MDQ symptom score was estimated at 29.9% (p<0.001), which was evenly distributed across its three principal components. Strong and significant genetic correlations were found between categorical diagnoses and most MDQ measures, especially impairment. Conclusion: The results support the MDQ as a dimensional measure of BSD. Furthermore, significant heritability and high genetic correlations between MDQ and categorical BSD diagnoses suggest a genetic continuity between dimensional and categorical measures of major mood disorders.