Impact of Human Melanopsin Gene (OPN4) Polymorphisms (I394T, P10L) on Nocturnal Melatonin and Daily Rhythms in Young Adults.

The present study investigates the impact of two missense SNPs in the human melanopsin gene OPN4 -I394T (rs1079610) and P10L (rs2675703)- on non-image-forming (NIF) physiological and behavioural outputs in healthy young adults under real-world conditions. Twenty-five healthy university students were genotyped and analysed under a C-allele dominant model for I394T and a T-allele dominant model for P10L. Over 8 days, participants underwent ambulatory monitoring of wrist skin temperature (WT), sleep, activity and light exposure, together with salivary melatonin assessment under five home-based lighting/time conditions and pupillary light reflex testing. I394T-C carriers exhibited a phase delay in habitual sleep and WT rhythms, reduced WT amplitude, greater internal desynchronization, and lower nocturnal melatonin concentrations under dim light compared to the TT group. Although behavioural and peripheral rhythms were delayed, circadian phase (DLMO) remained preserved, resulting in an increased phase angle of entrainment. On free days, they also showed greater melatonin suppression despite similar light exposure. In contrast, the P10L-T allele was not associated with significant differences in ambulatory, hormonal, or pupillary outcomes. Overall, the I394T variant, but not P10L, significantly associates with NIF physiology in young adults, likely by affecting the coupling between environmental light and downstream circadian outputs, independently of circadian phase. These findings also suggest that I394T-C carriers exhibit features of the circadian phenotype commonly observed in older cohorts, including reduced rhythm robustness and lower melatonin levels, and support a role for this variant in interindividual differences in light sensitivity and circadian function.