Circadian amplitude and CLOCK 3111 polymorphism predict morning leptin in Arctic residents, independent of photoperiod

This hypothesis-driven study tested whether circadian amplitudes of wrist temperature (WTA), physical activity (PAA), and light exposure measured by actigraphy predicted morning leptin in 64 Arctic residents, and whether the CLOCK 3111 polymorphism (rs1801260) modulated these predictions. Actigraphy measures (circadian amplitudes of WT, PA, and light exposure) and morning leptin concentrations were assessed across seasons with contrasting photoperiods. Multivariate regression models identified leptin predictors. Post-hoc analyses examined WTA–leptin relationships, considering CLOCK 3111 genotype and an exploratory leptin threshold of 13 ng/mL. A multivariate analysis adjusted for the photoperiod revealed significant negative associations between leptin and WTA (β = –0.344), PAA (β = –0.323) and sleep efficiency (β = –0.265) that were retained after further adjustment for age, sex and indigeneity. In the fully adjusted model, a larger normalized amplitude of blue light exposure (NA BLE) was associated with increased WTA (β = 0.256) and lower leptin (β = –0.171). The CLOCK 3111 polymorphism modulated the WTA – leptin relationship, with a strong negative correlation in TT individuals (r = –0.509) and a non-significant trend towards a positive association in CC individuals (r = 0.282), Δr = 0.791, z = 2.31, p = 0.021. In CLOCK 3111 TT individuals, those with a WTA <1°C had significantly higher odds (OR = 3.93, 95% CI: 1.69–9.17, p = 0.0015) and increased relative risk (RR = 2.70, 95% CI: 1.47–4.99, p = 0.0014) of having a morning leptin ≥13 ng/mL, compared to those with a WTA >1.5°C. Overall, the smaller circadian amplitude of WTA and PAA, the lesser sleep quality, and the smaller normalized amplitude of blue light exposure (NA BLE), independently of photoperiod, are associated with elevated leptin in Arctic residents. The CLOCK 3111 polymorphism modulates the WTA–leptin relationship. For CLOCK 3111 TT individuals, a small WTA (<1°C) may identify those at risk of elevated morning leptin (≥13 ng/mL), informing metabolic risk assessment in unique environments.