Abstract

Objective: The Circadian Locomotor Output Cycles Kaput (CLOCK) gene play an important role in
the maintenance of circadian rhythm and the regulation of sleep quality. Job stress has been found
to affect circadian rhythm mediated by the response of the hypothalamic–pituitary–adrenal axis.
There have been no previous reports on the combined effect of the CLOCK gene polymorphisms
and job stress on sleep quality. Therefore, we performed a cross-sectional study to investigate the
effects of CLOCK polymorphism genotypes, job stress, and their interactions on the sleep quality
in China.
Methods: We recruited 591 participants and 580 subjects remained eligible based on our selection
criteria. Their sleep quality and job stress were assessed using the Pittsburgh Sleep Quality Index
(PSQI) and Work Stress Scale, respectively. The genotypes of rs11932595 polymorphism were
determined with the polymerase chain reaction.
Results: Both job stress level and the genotype of rs11932595 were significantly associated with
sleep quality (p-value < 0.001 for stress and p-value= 0.003 for genotype). The G allele of
rs11932595 and high job stress were associated with a higher score on the PSQI. By logistic
regression, a high level of job stress was found to increase risk of poor sleep quality, independent
of confounding factors (odds ratio (OR) = 88.578, p-value=0.001). Similarly, a significant main
effect was found for G genotype on poor sleep (OR = 55.005, P<0.001). The interaction between
job stress and s11932595 polymorphism was significant(p-value =0.011). Stratified logistic
regression found significantly higher risk of poor sleep quality for high stress among A allele (OR =
8.420, p-value = 0.001) and for G allele among low stress (OR = 73.728, p-value = 0.001).
Conclusions: Job stress and CLOCK gene polymorphism are associated with poor sleep quality.
We have also provided evidence for the interaction of job stress and rs11932595 genotype on the
risk of poor sleep quality. Therefore, our data demonstrated a gene-environment interaction on
sleep and such mechanism should be exploited to develop effective intervention mechanism in the
future.

1. Introduction

Sleeping is an essential physiological process, necessary for our daily activity. Good sleep quality
helps to maintain physical and mental well-being. However, many studies have observed poor
sleep quality among population of different countries. (Knudsen, Ducharme et al. 2007, Mishima,
DiBonaventura et al. 2015, van de Straat and Bracke 2015)Recent studies have shown that poor
sleep quality is associated with psychological diseases ((Araghi, Jagielski et al. 2013)) as well as
metabolic and cardiovascular diseases (Van Cauter, Splegel et al. 2008, Sabanayagam and
Shankar 2010). Therefore, poor sleep quality is currently one of the leading health problems
around the world.

One of the important factors influencing sleep quality is job stress. A number of studies have
demonstrated the relationship between poor sleep and various types of job stress, such as high job
demand (Hanson, Chungkham et al. 2014), organizational inequality and effort-reward imbalance
(Rugulies, Norborg et al. 2009), low job control(Dong, Zhang et al. 2017) and low social support
(Kim, Kim et al. 2011). On the other hand, high support from immediate superior, frequent rewards
for well-done work, and high job control are associated with reduced odds of poor sleep (Eriksen,
Bjorvatn et al. 2008). These results clearly show that work environment that produces high arousal
and stress among employees is detrimental to their sleep quality.

In addition to job stress, genetic factors may also increase the risk of sleep problems. Sleep quality
is influenced by two interdependent mechanisms: the homeostatic mechanism and oscillations of
the circadian clock(Borbely, Daan et al. 2016). Therefore, it seems logical to investigate variants of
clock genes in relation to sleep phenotypes. In mammals, clock genes are involved in the 24 hour
molecular oscillations of the circadian system, and therefore may contribute to the regulation of the
sleep-wake cycle (Carpen, Archer et al. 2005). CLOCK forms part of the positive regulator of the
circadian system and acts as a transcriptional regulator that drives the expression of negative
elements (PER1, 2, and 3, and CRY1 and 2) of the feedback loop(Wulff, Porcheret et al. 2009).
Studies conducted in rodents showed that mutations in CLOCK gene is associated with disrupted
circadian rhythm and sleep(Vitaterna, King et al. 1994). However, there is no definitive conclusion
on the influence of CLOCK gene in sleep among human, and the scope of such research is rather
limited. To date, most studies investigate the effect of CLOCK gene polymorphism have focused
on a single polymorphism named rs1801260 or T3111C. Although large amount of research have
been devoted to the relationship between the variations in CLOCK gene and sleep phenotypes,
the mixture of positive and negative results suggests the need of further investigation. For
example, it was found that rs1801260 is associated with diurnal preference. More specifically, the
C allele carriers preferred eveningness(Katzenberg, Young et al. 1998). Contradictorily, Iwase et
al. (2002) found that 3111C allele frequency decreased among patients with delayed sleep phase
syndrome(DSPS), an extreme form of eveningness (Iwase, Kajimura et al. 2002). However, other
studies did not find a significant association of rs1801260 with sleep disuturbance(Robilliard,
Archer et al. 2002), or with diurnal preference and DSPS(Serretti, Gaspar-Barba et al. 2010).
Given the complexity of the influence of circadian genes on sleep, it is unlikely that one
polymorphism in the CLOCK gene can play a decisive role. Therefore, we suggest new research
possibilities by investigating a novel CLOCK gene polymorphism and its effects on sleep.

Only two previous studies have published results on the CLOCK rs11932595 polymorphism in
relation to sleep. Allebrandt et al. (2010) reported that the A allele is associated with long sleep
duration, while Vanderlindet al. (2014) found a significant association between G allele and self-
reported sleep difficulty but not objective measures of sleep. There have also been relatively few
studies associating this polymorphism with other diseases. The connection between rs11932595
and idiopathic recurrent spontaneous abortion(Hodzic, Lavtar et al. 2018), male infertility (Hodzic,
Ristanovic et al. 2013)and nonalcoholic fatty liver disease (Sookoian, Castano et al. 2007)have
been reported.

Most previous studies have highlighted the roles of job stress and CLOCK genes in sleep quality
separately. However, the relationship between these three parameters has rarely been explored
before. Investigating the gene-environment interaction(GxE) of CLOCK and stress on sleep might
provide further insight. Therefore, we carried out a study to examine the independent and
interactive effects of rs11932595 gene polymorphisms and job stress on sleep quality amongst
university faculty and staff in China.

2. Method

2.1 Participants

The subjects of this study were recruited from faculty and staff members of a university in Beijing.
They were selected based on 2 criteria：first, they must be currently employed by the university,
second, they do not have any past history of mental or psychiatric disorders. Informed consent
were obtained from all participants in written form. Out of the 591 responses received, 580 valid
subjects were selected based on the above criteria. Participants completed a basic questionnaire
comprising of questions on gender, age, educational background, job title and position, physical
and mental conditions. 378 subjects are willing to provide blood sample for genotyping. This study
was approved by the Ethnic Committee of Peking University.

2.2 Job Stress Measurements

Job Stress was measured using the Work Stress Scale developed by House and Rizzo(House
and Rizzo 1972). This questionnaire is composed of 11 items such as “I often feel worried about
my job” and “My work is a heavy mental burden.” Response to each item is rated on a scale of 1-6,
1 being completely disagree and 6 being completely agree. Therefore, the total score ranges from
11-66, with higher score corresponds to higher level of stress. We divided our sample according to
their stress scores. Subjects with a stress score below the sample mean (32.11) were placed in the
low stress group, and those above were placed in the high stress group.

2.3 Sleep quality Measurement and Grouping

Sleep disturbance was measured by Pittsburgh Sleep Quality Index (PSQI), a self-reported
questionnaire developed by Buysse(Buysse, Reynolds et al. 1989). The Mandarin Chinese version
was translated and its reliability and validity were verified in a study in 2005(Tsai, Wang et al.
2005). This questionnaire assesses sleep quality of the previous month using seven components:
subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep
disturbances, use of sleeping medication, and daytime dysfunction. Each component generates a
score from 0 to 3. The total score is the sum of each individual components. Lower score indicates
a better overall sleep quality. We categorized the sample into healthy or poor-sleep groups using 7
in the total PSQI score as a cut-off (i.e. those with a score of 7 or less are healthy, and those who
scored above 7 is considered as having poor sleep).

2.4 DNA extraction and SNP polymorphism testing procedures.

5ml venous blood sample was taken from each subject at morning fasting state. DNA from white
blood cells was precipitated and purified from cell lysate. The genotype of SNP polymorphism was
then identified using polymerase chain reaction(PCR). The full sequences of primers used in PCR
were devised and synthesized by Beijing Thinkout Sci-Tech Co. Ltd. and presented in
Supplementary Table 1.

2.5 Statistical Analysis

All data analysis were done using SPSS24.0. Data on total stress score, total PSQI score and
scores of each component of PSQI were presented as mean ± standard deviation. Difference
among these scores for the demographical variables was analyzed using general linear model.
The Hardy-Weinberg equilibrium (HWE) of rs11932595 in our sample was checked using the
calculator developed by Rodriguez(Rodriguez, Gaunt et al. 2009). We grouped the genotypes by
the risk allele (i.e. those homozygous in A and those with at least one G allele). General linear
model was employed to examine the difference of each component of PSQI scores between
different SNP alleles and between different stress groups. The main and interaction effects
between job stress level and genotype associated with the prevalence of poor sleep quality was
determined using logistic regression. These effects were further examined using crossover
analysis and stratified logistic regression. All odds ratios have been adjusted for confounding
demographical variables. Significance level of 0.05 was set for all hypothesis tests performed.

3. Results

3.1 Characteristics of the participants and their associations with sleep quality

Demographical data of participants collected from initial questionnaire are displayed in Table 1.
Out of the 580 individuals surveyed, there were 204 male participants (54%). Out of all the
participants, 197(34.0%)has a Ph. D degree, 243(41.9%) has a master degree, 108(18.6%) has a
Bachelor degree, and 21(3.6%) has a degree below the bachelor’s.

Characterization of the total stress score and the total PSQI scores according to age groups,
gender, education level, physical condition and mental condition are presented in Table 2. No
gender difference was found for the total PSQI score. PSQI scores differed significantly among
age groups, physical condition and mental condition(p<0.05). People aged 60 or above had a
much higher PSQI score than the others. Stress scores were found to differ significantly among
gender, age groups, physical and mental conditions (p<0.05). Male showed a higher stress level
than females. People aged 30-39 and 40-49 scored higher on the stress scale than the rest.

3.2. The HWE of CLOCK rs11923595 polymorphism among the subjects

Table 3 presented the result of the χ2 test for HWE. Our sample contains 311 subjects with AA
genotype(82.3%), 60 with AG genotype(15.9%) and 7 with GG genotype(1.9%). This distribution
deviated significantly from the Hardy-Weinberg equilibrium (p-value = 0.0492)

Table 1 Demographical Charateristics of the Participants

Characteristic Category Number Percentage

Gender Male 291 50.2

Female 284 49.0

Missing data 5 0.9

Total 580 100

Age 20-29 91 15.7

30-39 222 38.3

40-49 151 26.0

50-59 102 17.6

60 or above 9 1.6

Missing data 5 0.9

Educational Ph. D, 197 34.0

Background
Master 243 41.9

Bachelor 108 18.6

Below bachelor 21 3.6

Missing data 11 1.9

Position Administrative 267 46.0

Staff

Faculty 274 47.2

Missing data 39 6.7

Title Professor 69 11.9

Associate 120 20.7

Professor

Lecturer 69 11.9

Missing data 322 55.5

Physical Excellent 170 29.3

Condition
Good 331 57.1

Average 62 10.7

Poor 3 0.5

Missing data 14 2.4

Mental Excellent 222 38.3

Condition
Good 280 48.3

Average 42 7.2

Poor 5 0.9

Missing data 31 5.3

3.3. Comparisons of PSQI Scores across Different Job-Related Stress Levels and Genotypes

Differences of the PSQI score and each subcomponents according to the CLOCK polymorphism
rs11932595 genotype and stress groups are shown in Table 4 and 5, respectively. Sleep duration
and total PSQI score differed significantly between the genotype groups (p<0.05). G allele carriers
displayed a higher score in each of these components than A allele homozygotes. The high stress
group showed a significantly high PSQI score than the low stress group (p<0.001).

3.4. Interaction between Job Stress and the CLOCK s11932595 Polymorphism on Sleep Quality
 Table 2 Association of Demographical Charateristics with Stress and PSQI Scores

Characteristic PSQI
Stress

Gender

Male 32.86±10.811 5.06±2.868

Female 30.57±10.076 4.96±2.868

p-value 0.019 0.719

Age

<30 29.85±9.370 4.59±2.410

30-39 32.76±10.261 5.24±2.790

40-49 33.27±10.755 4.98±2.949

50-59 28.62±11.024 4.55±2.700

≥60 31.88±10.696 8.75±5.497

p-value 0.009 0.001

Educational Level

Ph.D. 32.43±11.394 4.79±2.995

Master 31.76±10.088 4.90±2.670

Bachelor 30.89±9.628 5.50±2.869

Below Bachelor 29.08±9.395 6.33±3.551

p-value 0.577 0.102

Physical Condition

Excellent 28.26±10.310 4.21±2.672

Good 32.95±9.795 5.26±2.667

Average 36.95±11.795 6.41±3.681

Table 3 The Hardy-Weinberg Equalibrium of rs1132595
Genotype Number Precentage
Poor 31.50±9.192 9.00±2.828
AA 311 82.3
p-value <0.001 <0.001
AG 60 15.9

Mental Condition
GG 7 1.9
2
Table 6 showed the main and interaction effect of job stress and CLOCK polymorphism on sleep
3.87
χExcellent 26.90±9.241 3.98±2.570

p-value
Good 34.62±9.482 5.63±2.639 0.0492
 quality. The main effect of job stress is stronger than that of CLOCK (AOR for G genotype =
55.005, p<0.001; AOR for high stress=88.578, p=0.001). There is a significant interaction between
these two factors on sleep quality (p=0.011).
The results of crossover analysis are presented in table 7. When compared to subjects with low job
stress and allele A, all the other groups(low stress and allele G, high stress and allele A, high
stress and allele G) were more likely to report poor sleep quality (p<0.001) .

Table 8 showed stratified logistic regression analysis. Taking low job stress as stratification factors,
we found higher risk of poor sleep among subjects with allele G than those with allele A (AOR =

Table 4 Association of PSQI total and components scores with job stress levels
sleep sleep subjective sleep sleep sleep daytime PSQI

latency duration sleep quality efficiency disturbance medication dysfunction

Job Low 0.50±0.66 0.46±0.72 0.83±0.68 0.18±0.48 1.07±0.26 0.05±0.31 1.07±0.91 4.15±2.39
stress

Number 244 244 244 244 244 244 244 244

High 0.77±0.88 0.58±0.72 1.27±0.73 0.35±0.75 1.18±0.40 0.07±0.42 1.75±0.94 5.99±3.05

Number of PSQI
Table 5 Association 215 total and components
215 scores
215 with Genotypes
215 of rs11932595
215 215 215 215
sleep sleep subjective sleep sleep sleep daytime PSQI

P-value latency
<0.001 duration
0.071 sleep
<0.001quality efficiency
0.003 disturbance
<0.001 medication
0.458 dysfunction <0.001
<0.001

Genotype effect
AA size 0.031
0.57±0.74 0.007
0.45±0.65 0.092
1.03±.73 0.019
0.23±0.60 1.11±0.32
0.029 0.06±0.37
0.001 1.42±1.00
0.120 4.87±2.61
0.103

Number 246 246 246 246 246 246 246 246

G/GA 0.75±0.84 0.88±0.92 1.23±0.63 0.34±0.67 1.16±0.42 0.11±0.41 1.61±0.87 6.07±2.97

Number 56 56 56 56 56 56 56 56

P-value 0.106 <0.001 0.061 0.218 0.350 0.413 0.194 0.003

effect size 0.009 0.052 0.012 0.005 0.003 0.002 0.006 0.030
73.728, p-value = 0.001) When stratified by allele A, high job stress showed a higher risk of poor
sleep than those with low work stress (AOR = 8.420, p-value <0.001). However, in the subjects
with allele G, there were no significant risk associated with job stress and poor sleep quality.
Among those who experience high level of job stress, there were no significant impact of genotype
on the prevalence of poor sleep.
AOR: adjusted odds ratio, CI: confidence interval. *: AOR for the interaction term is the ratio of
odds ratios
AOR: adjusted odds ratio, CI: confidence interval.

AOR: adjusted odds ratio, CI: confidence interval.

4. Discussion
Table 6 Main and Interaction effects of Genotype and Job stress
Variable AOR 95% CI p-value

Allele (G) 55.005 6.320-478.723 <0.001

Job Stress (High) 88.578 6.306-1244.242 0.001

Allele * Stress 0.324* 0.135-0.776 0.011

Table 7 crossover analysis of job stress and the rs119325295 allele on sleep quality
Job Stress Allele 1-7 8 and above AOR 95% CI p-value

Low A 119(96.0%) 5(4.0%) Reference Reference Reference

Low G 23(74.2%) 8(25.8%) 17.832 4.336-73.347 <0.001

High A 90(75.0%) 30(25.0%) 9.310 2.867-30.236 <0.001

High G 16(66.7%) 8(33.3%) 17.450 3.818-79.755 <0.001

Table 8 stratified logistic regression of job stress and the rs11932595 allele on sleep quality
Allele

A G AOR 95%CI p-
value

1-7 8 and 1-7 8 and

above above

Job Low 119(96.0 5(4.0%) 23(74.2%) 8(25.8%) 73.728 5.771- 0.001

stress 941.991
%)

High 90(75.0%) 30(25.0%) 16(66.7%) 8(33.3%) 1.912 0.638-5.731 0.247

AOR 8.420 0.985

95% 2.536-27.961 0.202-4.797

CI

p- 0.001 0.985
value
In this study, our findings indicate that job stress and the CLOCK gene are associated with sleep
quality. The subjects with high job stress level and/or the allele G on rs11932595 were more likely
to report poor sleep quality. Furthermore, our results indicate that there were significant main and
interaction effect between CLOCK genotype and job stress in the risk of poor sleep in a Chinese
sample of university faculty and staff. These effects were independent of confounding factors such
as age, gender, educational level, physical and mental health. This finding is consistent with a
previous study conducted by Li et al.(2015), who reported that a SNP in the Per2 gene interacted
with job stress to increase the risk of insomnia. Previous studies have also established a link
between CLOCK gene polymorphism and depression (Soria et al., 2010; Benedetti et al, 2013)
and that sleep problems are highly correlated with depression (Sivertsen et al., 2014). There have
also been large amount of research associating job stress with depression (Tsutsumi et al., 2001;
Clays et al., 2007; Zhong et al., 2009; Pflanz et al., 2006; Newbury-Birch et al., 2001). Therefore,
our findings may serve as important predictors for the prognosis of both poor sleep and
depression. To the best of our knowledge, this is the first study reporting the interaction between
CLOCK gene polymorphism and job stress in sleep quality.

4.1. Effect of job stress on sleep quality

Previous studies have demonstrated that job stress is a major factor in disturbing sleep
quality(Linton 2004, Jansson-Frojmark, Lundqvist et al. 2007, Song, Choi et al. 2017). In
accordance with these researches, our study demonstrated that sleep latency, subjective sleep
quality, sleep efficiency, sleep disturbance, daytime dysfunction and total PSQI scores in subjects
with high job stress were all significantly higher than those with low job stress. The results of
logistic regression further proved that participants with high job stress were at higher risk of
experiencing poor sleep quality than those with low job stress, after adjusting for confounding
factors. we believe that these effects in sleep disturbance are likely the result of cognitive and
physiological arousal due to activation of HPA axis under stress(Buckley and Schatzberg 2005).
Various studies have investigated the relationships between sleep and the HPA axis (Steiger
2002). For example, intravenous injection of CRH has been demonstrated to reduce slow-wave
sleep and rapid eye movement sleep(Holsboer, Vonbardeleben et al. 1988). Therefore, stress-
responsive hormones released during HPA axis activation can have a profound influence on sleep.

4.2. Effect of CLOCK gene polymorphism on sleep quality

There are relatively few studies which have investigated the association between the rs11932595
polymorphism and PSQI components. The results of our study indicated that the presence of the G
allele is associated with higher sleep duration and the total PSQI score. The result of logistic
regression showed that allele G was significantly increased the risk of poor sleep quality compared
to allele A. Two previous studies confirmed our results, showing that A allele is associated with
longer sleep duration and that G allele is associated with higher level of self-reported sleep
difficulty (Allebrandt, Teder-Laving et al. 2010, Vanderlind, Beevers et al. 2014). Although the HWE
was violated in our sample, the p-value is only slightly below the cut-off line of 0.05 and therefore
can be attribute to our small sample size. rs11932595 is a SNP that occurs within an intronic
region of the CLOCK gene. Therefore, it is difficult to identify the underlying mechanism that
connect this SNP with variation in sleep quality. It is possible that this polymorphism leads to an
alternative splicing pattern of the CLOCK gene, which could potentially affect the regulation of
circadian clock. Further experiments should be conducted to identify if this genetic variation
affects sleep quality via dysregulation of circadian clock.

4.3. Effect of the interaction between job stress and CLOCK polymorphism on sleep quality

Our findings provide new insight into the contribution of genetic and environmental interactions to
sleep quality. First of all, we found that the influence of job stress on poor sleep quality is stronger
than that of genotype. Secondly, there exists an interactive effect between these two factors. The
results of stratified logistic regression showed that subjects with high level of job stress were more
likely to report poor sleep than those with low job stress level among subjects with the A genotype.
Using low stress as the stratification factor, we found people with G allele have a significantly
increased risk of poor sleep. Interestingly, among the subjects with high level of stress, subjects
with A or G allele did not differ significantly in their prevalence of poor sleep. Similarly, high level of
job stress did not increase the risk of poor sleep when G allele is taken as the stratification factor.
Therefore, it can be concluded that high stress masks the effect of genotype and that job stress
level does not have a pronounced effect on sleep for G allele carriers. We also found that the
prevalence of poor sleep among people with both high stress and G allele is slight less than that of
people with G allele and low stress. Given that we have demonstrated a more dominant effect of
job stress than genotype, it seems that this result needs further validation. Contrary to our results,
Li et al.(2015) showed a stronger effect of Per2 genotype than job stress on the occurrence of
insomnia(Li, Huang et al. 2015). This difference may be attributed to different genes surveyed
( Per2 vs CLOCK) and/or different measures of sleep quality. Also, it should be noted that we have
a limited sample of subjects with G genotype(31 with low stress and 24 with high stress), we
suggest that future experiments with a larger sample of G genotype should be conducted in order
to clarify the interaction between this polymorphism and job stress.

Another interesting result is that we did not demonstrate an multiplicative effect of genotype and
job stress on sleep quality. The combined effect (AOR= 17.450) is less than the product of the
effect of the gene (AOR=17.832) and that of stress (AOR=9.310). This result contradicts a
previous study where this multiplicative effect was found between 5-HTTLPR and job stress on
insomnia(Jiang, Cui et al. 2016). One potential explanation of this contradiction is that both stress
and variation in the 5HTTLPR affect the homeostatic regulation of sleep, which enabled the effects
to occur synergistically. However, as the CLOCK gene polymorphism primarily affects the
circadian regulation of sleep, the disrupted homeostatic control due to job stress is therefore less
likely to add to the effect of genotype. This part of the analysis also suffered from a lack of G
genotype samples. Our results, therefore, should be interpreted with caution and should be further
validated in a larger sample if possible.

4.4. Study limitations

There are some limitations that should be improved upon in future studies. First, there are
relatively few subjects in some of our groups. For example, the category “poor sleeper with A
genotype and low stress” have only five cases. Increasing the numbers of these cases is required
to verify the results in future study. Secondly, sleep quality was only evaluated using subjective
questionnaires. An objective measure such as polysomnographic recordings could be obtained to
substantiate the present findings. However, such an effort is both time-consuming and costly given
the large sample size of our study. Similarly, in order to measure stress level more accurately, an
objective index of job stress, like cortisol level, could have been applied. Third, some confounding
factors related to sleep quality, such as alcohol consumption level and exercise, were not
considered in this study. Several previous studies have identified the effect of alcohol on sleep
(Ebrahim, Shapiro et al. 2013, Park, Oh et al. 2015). Exercise have also been found to improve
sleep quality(Baron, Reid et al. 2013). Therefore, inclusion of these variables may strengthen our
conclusion. Finally, there were several sources of sample bias in this study. For example, some
subjects did not agree to provide blood sample and therefore cannot be genotyped. Those who
failed to complete the sleep and/or stress questionnaire were also excluded from our analysis.

5. Conclusions

In summary, this is the first study to investigate the interaction between job-related stress and
CLOCK gene polymorphism in sleep quality among Chinese university faculty and staff. We found
that the G allele of rs11932595 was a risk factor in poor sleep quality, and job stress increased the
risk of experiencing poor sleep. Given these results, we believe that the CLOCK gene has the
potential to serve as a biomarker for evaluating genetic traits of sleep and as a research target to
understand the mechanism underling the occurrence of sleep disorders. Also, sleep disturbance
have become an important issue among the working population due to the increasing prevalence
of job stress. Therefore, predicting sleep and circadian phenotypes based on genetic factors may
be helpful in identifying people prone to sleep disorder and developing interventions to improve
quality of life.
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