Genetic Association of the PERIOD3 (Per3) Clock Gene with Bipolar Disorder.

Objective: Circadian rhythms have been linked to psychiatric disorders such as Depression and Bipolar Disorder (BD). Given previous evidences of sleep/circadian disturbances as well as the genetic susceptibility for BD, we decided to investigate the possible link between the PERIOD3 (Per3) circadian gene and BD.

Methods: This is a genetic association case (BD) vs. control study of the Per3 gene. We further subdivided our BD sample into "good sleepers" (PSQI ≤5) and "poor sleepers" (PSQI>5) according to the Pittsburgh Sleep Quality Index (PSQI) global score, and then we assessed genetic association of the Per3 gene with sleep quality in the BD group.

Results: There were 209 cases and 213 controls in our sample. The GT genotype of the SNP rs707467 significantly associated with BD (χ=8.80; p-value=0.01; adjusted residual=±2.6). We also found significant association of the SNP rs10462020 allele T with BD (χ=5.81; p-value=0.01) as well as the genotype TT (χ= 6.01; p-value=0.04; adjusted residual=±2.4).

Conclusion: In this study we demonstrated evidences of genetic association between the Per3 gene and BD. The results of association between the Per3 gene and BD in our sample may bring additional evidence to the former findings of association between the Per3 gene and BD.