Table 1.

Main polymorphism of clock genes and their association in bipolar disorder.

Clock gene	Polymorphism	Association found in bipolar disorder	References
PER3	rs57875989	Extreme morning and early onset	Dijk and Archer (58)
		Extreme eveningness and later onset
PER 2	rs934945	Diurnal preference for eveningness	Song et al. (59)
CLOCK	rs10462028	Association with BD aetiology	Nievergelt et al. (60) Dmitrzak-Weglarz et al. (61) Soria et al. (62)
	rs11932595	Sleep disorders	Maciukiewicz et al. (63)
	rs1801260	Early stress, history of suicide attempt and persistence of the idea of suicide	Benedetti et al. (64) Bollettini et al. (65)
	rs11932595	More depressive episode and appetite disorder	Maciukiewicz et al. (63)
	rs1801260	Influence on sleep pattern, daytime preference, age at onset, and response to treatment	Bollettini et al. (65)
ARNTL (BMAL1)	rs2279287 rs1481892 rs1982350	Seasonal pattern Higher susceptibility to the disease	Geoffroy et al. (66) Rajendran and Janakarajan (67)
TIMELESS	rs2291738 rs10876890	Suicide attempts Insomnia	Pawlak et al. (68)
PPIEL*	Lower methylation level	Altered dopaminergic transmission or neuroendocrine system functions	Kuratomi et al. (69)
NR1D1 promoter	rs2071427	Good response to treatment	McCarthy et al. (70)
CRY1	rs8192440	Good response to treatment	McCarthy et al. (70)
GSK-3β	rs6438552	Robust and additive response to treatment if associated with NR1D1 (rs2071427)	Oliveira et al. (71)

ARNTL (BMAL1), Aryl hydrocarbon receptor nuclear translocator like protein-1; CRY 1-2, Cryptochrome circadian regulator; GSK-3β, Glycogen synthase kinase-3; NR1D1, Nuclear receptor subfamily 1 group D member 1; PER3, Period circadian regulator-3; PPIEL, E-like peptidilprolil isomerase; TIMELESS, Timeless Circadian Clock. *pseudogene.