Several circadian genes have been found to be associated with bipolar disorders: at least three studies have reported positive associations for each of CLOCK, NPAS2, ARNTL1, NR1D1, PER3, RORB and CSNK1epsilon.
The findings that have gained support indicate that genetic variants of RORA (rs2028122) and CRY1 (rs2287161) associate with depressive disorder, those of RORB (rs7022435, rs3750420, rs1157358, rs3903529) and NR1D1 (rs2314339) with bipolar disorder, and those of NPAS2 (rs11541353) and CRY2 (rs10838524) with seasonal affective disorder or winter depression.
Such connections to circadian genes such as CLOCK, ARNTL1, NPAS2, PER3 and NR1D1 have been repeatedly demonstrated for bipolar disorders, and to a lesser extent for recurrent depressive disorders and seasonal affective disorders.
Using lymphoblastoid cell lines from patients with BD, we found that both the NR1D1 and GSK3β variants are associated with functional differences in gene expression.