A potential limitation of this study may be the sole use of BDI subjects, since TEMPS-A data for controls was not available. However, this has enabled us to examine the genetic determinants of temperament within the context of BD. Another potential limitation is that some subjects may have been manic or depressed at the time of assessment, while others were euthymic. Though the TEMPS-A is designed to assess temperament as a lifelong characteristic with the subscales demonstrating good stability over time (29–30), it is possible that the subject’s self-assessment might be influenced by state at the time of testing. In the absence of quantitative manic or depressive symptom ratings, we used the GAF score as a covariate in the association analyses to control for state at the time of testing. To assess the possible effect of state and the effectiveness of the GAF score as a covariate, we compared subjects who met criteria for current mania or depression with those that were euthymic based on the DIGS interview (see Figure S1 and Table S3). Euthymic subjects comprised 79% of the