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Study on the relationship between

circadian polymorphism,
depression and sleep
Main Results and Discussion
Preliminary Analysis
• In order to identify potential SNPs affecting sleep and
depression, a correlation analysis was conducted
involving every SNP in the database, SDS score and
PSQI total score. The Pearson’s correlation
coefficients between rs12649507 and the other two
variables were significant.

• The demographical variables were tested for their


effect on depression and sleep using ANOVA. Mental
health was found to significantly related to depression
and sleep. This was controlled for in later studies.
Table 5 Association of SDS score. PSQI total and components scores with Genotypes of rs11932595

sleep latency sleep duration subjective sleep sleep efficiency sleep disturbance sleep medication daytime PSQI Depression

quality dysfunction

1.10±0.295 0.04±0.308
Genotype AA 0.45±0.665 0.40±0.565 0.96±.664 0.15±0.411 1.17±0.975 4.27±2.172 32.89±8.042

Number 105 105 105 105 105 105 105 105 105

G/GA 0.69±0.791 0.59±0.779 1.15±0.727 .30±0.705 1.14±0.366 0.06±0.335 1.63±0.924 5.56±2.764 35.31±8.027

Number 182 182 182 182 182 182 182 182 182

P-value 0.009 0.027 0.027 0.056 0.257 0.576 <0.001 <0.001 0.014

effect size 0.023 0.017 0.017 0.013 0.005 0.001 0.052 0.056 0.021
Logistic Regression
Category AOR 95% CI p-value

G genotype 2.140 1.211-3.782 0.009

Depression 1.065 1.027-1.104 0.001


Mediation Analysis
What can we learn from

this?
A SNP on the CLOCK gene is related to both depression
and sleep.

• There is a bilateral relationship between circadian rhythm


and depression

• Sleep is controlled by circadian and homeostatic regulation,


while circadian gene plays a role in both.

• Hence circadian genes must be important to both


depression and sleep

• So nothing really that surprising


What’s New?
• More evidence on the effect of SNP on depression: Results
linking circadian genes to depression were obtained using
mutation/deletion. Analysis on SNPs is limited and with
mixed results

• A novel SNP: rs12649507 was never related to depression,


while only one study investigated its effect on sleep.

• Better Statistics: Both ANOVA and logistic regression


confirmed this relationship. Also few studies have
connected SNP with both depression and sleep. This is the
first study to demonstrate a mediation effect.
Limitations
• Did not obtain any objective data on depression and
sleep. Hard to achieve due to large sample size.
Also, objective measures of depression are difficult
and may not be reliable.

• Small population of depressed subjects. Only 21


participants are mildly depressed, no one
moderately or severely depressed according to
SDS. Need to recruit these subjects for more
complete analysis.
What to do next?
• What exactly does this SNP affect? Does it change the RNA
expression level or the RNA structure? Does it have any
effect on the CLOCK protein structure or function? Answers
to these question may lead to better understanding of the
mechanism of depression and sleep disturbance

• What other factors are involved in depression and sleep?


Common knowledge says “stress”. Our preliminary analysis
agree, but we are unable to find any genetic basis.

• Physical and mental health correlated with stress,


depression and sleep. Need to find a model that connects
these variables.

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