Melanopsin Gene Variations Interact With Season to Predict Sleep Onset and Chronotype

Abstract

The human melanopsin gene has been reported to mediate risk for seasonal affective disorder (SAD), which is hypothesized to be caused by decreased photic input during winter when light levels fall below threshold, resulting in differences in circadian phase and/or sleep. However, it is unclear if melanopsin increases risk of SAD by causing differences in sleep or circadian phase, or if those differences are symptoms of the mood disorder. To determine if melanopsin sequence variations are associated with differences in sleep-wake behavior among those not suffering from a mood disorder, the authors tested associations between melanopsin gene polymorphisms and self-reported sleep timing (sleep onset and wake time) in a community sample (N = 234) of non-Hispanic Caucasian participants (age 30–54 yrs) with no history of psychological, neurological, or sleep disorders. The authors also tested the effect of melanopsin variations on differences in preferred sleep and activity timing (i.e., chronotype), which may reflect differences in circadian phase, sleep homeostasis, or both. Daylength on the day of assessment was measured and included in analyses. DNA samples were genotyped for melanopsin gene polymorphisms using fluorescence polarization. P10L genotype interacted with daylength to predict self-reported sleep onset (interaction p < .05). Specifically, sleep onset among those with the TT genotype was later in the day when individuals were assessed on longer days and earlier in the day on shorter days, whereas individuals in the other genotype groups (i.e., CC and CT) did not show this interaction effect. P10L genotype also interacted in an analogous way with daylength to predict self-reported morningness (interaction p < .05). These results suggest that the P10L TT genotype interacts with daylength to predispose individuals to vary in sleep onset and chronotype as a function of daylength, whereas other genotypes at P10L do not seem to have effects that vary by daylength. A better understanding of how melanopsin confers heightened responsivity to daylength may improve our understanding of a broad range of behavioral responses to light (i.e., circadian, sleep, mood) as well as the etiology of disorders with seasonal patterns of recurrence or exacerbation. (Author correspondence: [email protected])

Keywords:

• Chronotype
• Genetics
• Melanopsin
• Seasonal affective disorder
• Sleep

ACKNOWLEDGMENTS

We are grateful to Janet Lower for her assistance in data collection and data management. We are grateful to Dr. Ahmet Bakan from the University of Pittsburgh Department of Computational and Systems Biology for his advice regarding the possible structural consequences of the P10L mutation.

Declaration of Interest: This work was supported by NIH grant P01 HL040962 (S. B. Manuck).

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.