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Background: CLOCK 3111T/C has been shown to be closely associated with morningness-eveningness, such as sleep-wake rhythms in healthy humans. However, previous studies examined the physical activity (PA) in a single day, and no study has investigated the relationships between CLOCK 3111T/C polymorphism and PA for an entire week. It was hypothesized that the CLOCK 3111T/C polymorphism might be associated with diurnal PA patterns, especially on the weekends., Methods: Eighty-one university students (male, n = 14; female, n = 67; age, 20.4 ± 2.9 years) wore a digital accelerometer for 7 successive days, including the weekend, to collect hour-by-hour objectively-measured PA. CLOCK 3111T/C polymorphism was assessed using the oral mucosa. During the study, participants recorded their wake time and bedtime each day. Furthermore, lifestyle-related variables (i.e. morningness-eveningness, habitual meal and sleep timings) were collected using questionnaires. Linear mixed-effects models assessed the association of polymorphism (TT carriers vs. TC+CC carriers) with wake time and bedtime as well as daily PA throughout the week (time)., Results: TT carriers had an earlier wake time (weekly mean: 44 min [95% CI, -82 to -5 min], time interaction: p = 0.026) and bedtime (weekly mean: 30 min [95% CI, -61 min to - 15 s], time interaction: p = 0.048) than TC+CC carriers. Furthermore, TT carriers' wake time and bedtime on Saturday were significantly later than on other days (gene interaction: all p < 0.05). On Saturday, the hour-by-hour PA in TT carriers was significantly greater than that in TC+CC carriers (hourly mean 1.7 min [95% CI, 0.2 to 3.4 min], time: p < 0.001, group: p = 0.028, interaction: p = 0.155)., Conclusions: CLOCK 3111T/C polymorphism may be associated with objectively measured hour-by-hour PA only on Saturday. Academic/social obligations may mask the genetically determined biological rhythm of PA on weekdays., (Copyright © 2022. Published by Elsevier Inc.)

A number of genome-wide association studies have investigated sleep phenotypes and disorders in humans. However, the contribution of genetic variation to sleep problems in Japanese populations has remained unclear. Sleep-onset problems are the most common symptom of insomnia. Here, we examined the relationship between single nucleotide polymorphisms (SNPs) of BMAL1 (ARNTL1), CLOCK, CRY1, CRY2, and PER2, which are genes involved in the clock mechanism, and sleep-onset problems in a Japanese general population. This study included 1,397 subjects aged ≥ 40 years who participated in an annual health check-up in Yamagata Prefecture. A total of 80 SNPs of 5 circadian clock genes were analyzed. Multivariate logistic regression analyses identified variant rs11113179 in CRY1 and variants rs1026071 and rs1562438 in BMAL1 as genetic risk factors for sleep induction disorder. These findings suggest that CRY1 and BMAL1 polymorphisms are related to sleep-onset problems in a Japanese general population. However, none of the SNPs remained significant at a stringent level of multiple correction.

Using large-scale objective sleep data derived from body acceleration signals of 68,604 Japanese residents ranging from adolescents to the elderly (10-89 years old), we found significant age- and gender-related differences in sleep properties (timing, duration, and quality) in real-life settings. Time-in-bed and total sleep time (TST) showed a U-shaped association with age, indicating their decrease in adulthood following their increase in the elderly. There was a remarkable shift in sleep phase toward earlier bedtime and earlier wake time with increasing age (> 20 years), together with worsening of sleep quality, which is estimated by sleep efficiency (SE) and wake time after sleep onset. Gender comparisons showed that TST was shorter in women than in similarly aged men, which is much evident after the age of 30 years. This was associated with later bedtimes and greater age-related deterioration of sleep quality in women. Compared to men in the same age group, women over age 50 demonstrated a greater reduction in SE with aging, due mainly to increasing durations of nighttime awakening. These differences can be attributed to several intricately intertwined causes, including biological aging as well as socio-cultural and socio-familial factors in Japan. In conclusion, our findings provide valuable insights on the characteristics of Japanese sleep habits.

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: In our previous studies, we found that the Ile394Thr SNP in the melanopsin gene (OPN4) was functionally associated with the pupillary light reflex. This indicates the possibility that OPN4*Ile394Thr is associated with other non-image forming responses. The aim of this study was therefore to determine whether OPN4*Ile394Thr is associated with sleep/wake timing., Methods: A total of 348 healthy Japanese university students participated in this study. Scalp hair was used to genotype the Ile394Thr SNP of OPN4. Sleep habits, including bedtime, wake time and sleep duration, were assessed separately for weekdays and weekends. A total of 328 samples, including 223 samples with TT genotype, 91 with TC genotype and 14 with CC genotype, were used for statistical analysis. No significant difference in age or male/female distribution was found among the three genotype groups., Results: There was no significant difference in circadian preference among the genotype groups. During weekdays, bedtime, wake time and midpoint of sleep for CC subjects were significantly later than those for TT and TC subjects. However, there was no difference between TT and TC subjects in any of their sleep habits. During weekends, bedtime of CC subjects was significantly later than those of TT and TC subjects, and the midpoint of sleep of CC subjects was significantly later than that of TC subjects., Conclusions: Our findings demonstrated that OPN4*Ile394Thr is associated with sleep/wake timing. We also found that the sleep/wake timing of subjects with the CC genotype was later than that of subjects with the TT or TC genotype.

Sleep timing is influenced by the circadian system. Morningness-eveningness (ME) preference in humans is affected by the free-running period, which is determined by circadian clock-relevant genes. In this study, we investigated association between the 3111T/C polymorphism in the 3'-flanking region of hClock (Homo sapiens Clock homolog) and ME preference in 421 Japanese subjects. The Horne-Ostberg ME questionnaire (MEQ) scores showed normal distribution, with mean score of 51.2 +/- 1.4 (range, 25-73), and scores were positively correlated with sleep onset time (r = 0.541, P < 0.001) and wake time (r = 0.513, P < 0.001). MEQ scores were significantly lower in subjects with 3111C/C (n = 12) than in subjects with 3111T/C (n = 106, P < 0.001) or 3111T/T (n = 303, P < 0.001), suggesting a stronger eveningness preference in 3111C/C homozygotes. This group also showed significantly delayed sleep onset (P < 0.001), shorter sleep time (P < 0.001), and greater daytime sleepiness (P < 0.001) in comparison to parameters in the subjects with the 3111T allele. There was no significant difference in any of these parameters between the 3111C/T and 3111T/T genotypes. The influence of the 3111T/C polymorphism on ME preferences in Caucasian populations remains controversial. The present findings in a Japanese population sample, which should have a relatively low risk of population stratification effects, suggest the significance of the association of the 3111C/C allele of hClock with evening preference., ((c) 2004 Wiley-Liss, Inc.)