Circadian rhythm disruption in bipolar disorder: Mechanisms, clinical significance, and rhythm-oriented interventions

Table 1 Effects of multiple genes on the pathogenesis of bipolar disorder

Gene	Type	Variation	Effect	Strength
CLOCK	Core clock gene	ClockΔ19, SNPs (rs1801260C)	Simulated several core characteristics of BD	Highly correlated
BMAL1		SNPs, hypermethylation	Increased the susceptibility of BD and participated in shaping its clinical phenotype	Highly correlated
PER2		SNPs (rs2304672G)	Significantly increased the risk of BD	Significant correlation
PER3 VNTR		5/5 repeat genotype	Reduced the risk of BD	Significant correlation
CRY1		R263Q mutation, risk allele	Caused abnormal circadian rhythm pattern and affected BD	Significant correlation
REV-ERBα		Downregulated expression	Induced extensive apoptosis of NPC in patients with BD	Significant correlation
AKAP11	Other genes	Heterozygous mutation	Significantly increased the risk of BD	Correlation

SNP: Single nucleotide polymorphism; BD: Bipolar disorder; NPC: Neural progenitor cell.