CLOCK genotype modulates associations between blue light exposure and circadian activity amplitude

Background Circadian disruption is linked to adverse health outcomes, but individual susceptibility to light-based timing signals remains unclear. This study assessed how the CLOCK rs1801260 polymorphism modulates the impact of dynamic light exposure and prior SARS-CoV-2 infection on objective physical activity (PA) rhythmicity. Methods 116 adults (75 COVID+) underwent 7-day wrist actigraphy with blue light recording (Tyumen, Russia, 57°N). Cosinor-derived PA parameters (MESOR, amplitude [A], A/M ratio, acrophase) and non-parametric indices assessed rhythmicity. Regression/ANCOVA examined NA_BLE × CLOCK TT vs non-TT × COVID status interactions, controlling for age/sex/BMI. Results Poor light hygiene (Normalized Amplitude of Blue Light Exposure, NA BLE < 1) delayed the acrophase and reduced PA amplitude. Specifically, CLOCK rs1801260 TT homozygotes with NA BLE<1 had a reduced absolute ( p = 0.032) and normalized ( p = 0.003) PA amplitude. CLOCK rs1801260 TT genotype with NA BLE < 1 exhibited reduced PA amplitude compared to C-carriers (β = -0.483, p = 0.017, η² = 0.201) after adjusting for age, sex, and COVID-19 status. A compounding negative effect was noted in TT carriers with both NA BLE < 1 and COVID-19 history, showing an even smaller PA amplitude than C carriers with no history of COVID-19 ( p = 0.036). Conclusion These findings reveal a triple-hit model where genetic susceptibility (CLOCK TT), environmental insult (poor light hygiene), and prior systemic illness (COVID-19) synergistically disrupt circadian activity rhythms. They underscore the need for personalized chronotherapy integrating genetic profiling and post-viral health status.