. 2024 Aug 19;6(3):446–467. doi: 10.3390/clockssleep6030030

Table 2.

Studies reporting the link between circadian gene mutations and substance use disorders.

Circadian Genes	Study Subject and Genetic Mutations	Association with Disordered Substance Use	Reference
PER2	Humans (Swedish adolescent boys); SNP 10870 (A/G)	Increased alcohol consumption and sleep problems	[170]
PER1	Mice; mPer1-mutant, Humans (adolescents); SNP rs3027172	Higher stress-related alcohol consumption	[171]
PER2	Mice; Per2^Brdm1 mutant	Increased alcohol intake and elevated glutamate concentration	[172]
PER1	Rats; PER1::LUC transgenic	Chronic alcohol consumption leading to higher Per1 expression in adrenal and pituitary glands	[173]
PER1/PER2	Mice; Per1^Brdm1, Per2^Brdm1, Per1Per2 ^Brdm1 mutant	Increased ethanol intake and reinforcement behavior	[174]
CLOCK	Mice; homozygous Clock mutant (Clock/Clock)	Increased cocaine reward and higher dopamine excitability	[167]
CLOCK	Mice; Clock mutant (Clk^Δ19/Clk^Δ19)	Increased cocaine reward and increased VTA dopaminergic activity	[175]
CLOCK	Mice; Clock mutant (Clk^Δ19/Clk^Δ19)	Increased ethanol intake and higher dopaminergic and glutamatergic activity	[176]
CLOCK	Humans; reduced expression of Clock	Chronic alcohol dependence	[177]
Circadian Clock Genes	Humans (Finnish general population)	Variants in ARNTL, ARNTL2, ADCYAP1, VIP show association with alcohol abuse and social drinking; DRD2/ANKK1 and NPY is related with alcohol dependence	[178]

Abbreviations: SNP: Single nucleotide polymorphism; VTA: Ventral tegmental area.