The lengthened circadian rhythm observed in Afh mice results from a Cys358Ser substitution in the protein encoded by Fbxl3. Using three genome-wide association data sets including more than 4,000 cases and 5,000 controls, we found that on a combined analysis, variation in FBXL3, the human orthologue of Fbxl3 was associated with bipolar disorder. The gene discussed is FBXL3; the disease is bipolar disorder.