Association Analysis of Nuclear Receptor Rev-erb Alpha Gene (NR1D1) with Mood Disorders in the Japanese Population

Several investigations have suggested that alterations in circadian rhythms may lay the foundation for the development of mood disorder (bipolar disorder and major depressive disorder). Recently, the nuclear receptor Rev-erb alpha was reported to be related to circadian rhythms, and was shown to be involved in the biological action of lithium in vitro. These evidences indicate that the nuclear receptor Rev-erb alpha gene (NR1D1) is a good candidate gene for the pathogenesis of mood disorders. To evaluate the association between NR1D1 and mood disorders, we conducted a case-control study of Japanese samples (147 bipolar patients, 322 major depressive disorder patients and 360 controls) with three tagging SNPs selected by HapMap database. One SNP showed an association with bipolar disorder in females. After Bonferroni correction for multiple testing, however, this significance disappeared. No significant association was found with major depressive disorder. In conclusion, our findings suggest that NR1D1 does not play a major role in the pathophysiology of mood disorders in the Japanese population.