What role does CLOCK play in fatigue?

CLOCK (Circadian Locomotor Output Cycles Kaput) is a core circadian clock gene. Variants in CLOCK can influence circadian rhythms and have been associated in studies with sleep disturbances, fatigue, and metabolic issues. However, the effects of individual SNPs are typically small and heavily modulated by environmental factors such as light exposure, sleep hygiene, and stress. A direct causal link between a CLOCK variant and clinically significant fatigue is not established. Evidence is primarily mechanistic and from GWAS, not from interventional trials. Consumer DNA tests like MyBody-X can detect such variants, but interpretation remains speculative. Persistent fatigue warrants medical evaluation for multifactorial causes (e.g., iron deficiency, thyroid dysfunction, sleep apnea). The predictive value of a single gene is limited.