We have explored the use of temperament, as assessed by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), as a quantitative phenotype for BD that may define more homogenous subgroups of patients when assessed within a BD sample. The TEMPS-A is a self-report questionnaire designed to quantify temperament and assess lifelong, milder aspects of bipolar symptomatology (24–25). The five temperaments defined by this scale (hyperthymic, dysthymic, cyclothymic, irritable, and anxious) have been implicated in various affective disorders, and several have shown evidence of heritability and familiality in BD (4,11–13,15,18,26). The reliability and internal consistency of the TEMPS-A is well documented, and the temperaments have demonstrated stability over time, with one study reporting stability up to six years (23,27–30). We report the results of our genome-wide association (GWA) analyses of these temperaments in 1,263 unrelated bipolar I subjects and the identification of several genes that may predispose to BD through their modulation of temperament, as well as define subgroups of BD patients with similar clinical features and courses of illness.
