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CLOCK gene and sleep disturbance

Discussion in 'Genetic Testing and SNPs' started by roxie60, Aug 3, 2013.

  1. roxie60

    roxie60 Senior Member

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    I just came across this one and I know many of us struggle with sleep disturbances. I'm just curious if we can gather some SNP info and see if this gene / SNPs could also be markers or thy just might be comorbid (I think that is the term). This is just a thread for those wanting to contribute to researching CLOCK genes/SNPs and see if there is a correlation to our experiences. Disclaimer, I'm no expert so take any info provided on thread as is, not claiming it is correct.

    I stumbled on the CLOCK gene (isnt that a cute name for gene potentially associated with sleep issues)
    in this study http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044192/

    Here are two SNPs discussed, let me know if you find anymore that seem relevant. Post your results if you want to share.

    CLOCK rs3749474 Risk allele (C), I'm CC
    CLOCK rs3736544 risk allele (A), I'm AG (note T=A ifusing 23andME which I am)
     
    Beyond, taniaaust1 and Valentijn like this.
  2. roxie60

    roxie60 Senior Member

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  3. roxie60

    roxie60 Senior Member

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  4. roxie60

    roxie60 Senior Member

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  5. bel canto

    bel canto Senior Member

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    Roxie - I have the same alleles - CC and AG, and I have severe problems with my sleep.
     
  6. roxie60

    roxie60 Senior Member

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    thanks for sharing bel, I have no idea if this is relevant to our search for answers but thought it might prove interesting and hopefully provide some possible reasons for our experiences with sleep disturbances. Sadly have found no answers, options to resolve.

    Here is one more

    CLOCK rs1801260 risk allele A (I'n not sure really), I'm AG

    There also is evaluation of PER2 and PER3 genes impacting sleep but not found enough info yet.
     
  7. Valentijn

    Valentijn Activity Level: 3

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    I'm and CT and GG on those two, and AG on rs1801260.

    I usually don't have sleep problems unless there's pain or other external issues (or severe jet lag).
     
  8. ukxmrv

    ukxmrv Senior Member

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    I'm

    rs3749474 CT
    rs3736544 GG
    rs1801260 AG

    Sleep is OK for me. I'm a night owl though (family trait)
    and the things that keep me awake after that are pain and going to the loo all the time.

    Thanks Roxie, I'll have a read now of the links you posted
     
  9. bel canto

    bel canto Senior Member

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    rs1801260 is AG for me, also.

    What kind of sleep issues do you have, Roxie? My major problem is a delayed phase syndrome - inability to go to sleep until very late.
     
  10. Bluebell

    Bluebell Senior Member

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    I spent some time looking into the PER genes the other day, but the relevant factors about those genes can't be looked up as single SNPs, which makes it harder to figure out in one's own genetic data.

    This is from a newspaper article of 6 years ago:

    "Researchers believe 10 per cent of the population are extreme owls, 10 per cent are extreme larks and the remaining 80 per cent fall in between.
    And according to experts, it's genes rather than laziness.
    Scientists have long known that early and late risers have genetic differences. A study from the University of Surrey found that extreme larks are more likely to have a long version of a gene called Period 3, while extreme owls are more likely to have a shorter version, leading to physiological differences.
    Professor Angela Clow from the University of Westminster in London found that early risers had higher levels of [morning] cortisol, the body's main stress hormone, than the alarm-clock refuseniks."
    http://www.theage.com.au/news/health/night-owls-wise-up/2007/08/29/1188067176422.html

    There are several studies on pubmed that mention these genes.

    In the end, I gave up trying to figure out how to look at my Per genes because I already know I'm one of the 10% of extreme night owls!

    ---
    For the CLOCK rs numbers that Roxie60 listed above, I am disappointingly mainstream:

    rs3749474 CT - C is ancestral allele - looks like about 40% of all people have CT
    rs3736544 GG - G is ancestral allele - broadly about 50% of all people have GG
    rs1801260 AG (CT) - T is ancestral allele - perhaps about 40% of all people have CT
     
  11. ukxmrv

    ukxmrv Senior Member

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    I joined the B Society when it first appeared and still get their email newsletters. (it's mentioned in that AGE newspaper article).
     
  12. roxie60

    roxie60 Senior Member

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    bel canto For psat few years insomnia, then last year and half started having interupted sleep, usally woke up every two hours, body vibrating/tingling, muscles twitching. Had difficulty getting to sleep before 1AM. Very little dreaming. Then in March went on estridiol patch low dose and for the first time in so long I was able to go to bed like a normal person (1030-11P) and wake up about 630. It didnt last long :(. For the last month and a half I'm back to delayed sleep, cant seem to sleep until around 4-6AM. It has never been refreshing sleep (I dont wake up energetic, but not always fatigued either) . Seem to be waking up 2-3 times again. Also notice I have no appetite until late evening til early morning. It is bizarre and frustrating especially since I feel the pressure of needing to go back to work. I am just so tired all the time, no stamina easily fatigued. Times I feel as though my body is dying one cell at a time, I sense my body needs someting desparately and has for some time but I am at a loss to figure it out. Lately the chest pressure has returned but when take BP it is usualy ok although resting pulse can be high at times. I am wondering if these vitamins are making me more sick sometimes. I'm afraid to eat food and vitamins.
     
  13. bel canto

    bel canto Senior Member

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    Sorry to hear you're having such a rough time. Sleep issues are so friggin hard to find treatment for.

    I like your description of feeling like your body needs something desperately, and that the cumulative effects can be frightening. It's that feeling of going downhill that is most disheartening for many of us.

    Just a thought - the body vibrating/tingling and muscle twitching sort of sounds like a breathing issue. When I'm breathing too fast or too deep, I'll get those symptoms, and as soon as I slow my rate of breathing down, they stop. Have you asked a doc about that? Might be worth mentioning.
     
  14. roxie60

    roxie60 Senior Member

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    the tingling vibrating happens when awake also
     
  15. Aileen

    Aileen Senior Member

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    roxie60
    I haven't read the articles yet but just looked up my SNPs in 23andMe :
    CLOCK rs3749474 -- I'm a CC
    CLOCK rs3736544 -- I'm AG

    I also have severe sleep issues. Currently on amitriptyline partly to get to sleep (and for migraines). At the very beginning of this illness I was sleeping 20hrs a day but as with most of us this ended after a few years. After that I had different problems: day and night would get mixed up, or I'd be sleeping all afternoon etc...

    Then, I got to the point where I had a hard time getting to sleep at anytime and had almost stopped sleeping a few months ago. I'd get 4 to 5 hours sleep total over a 72hr period. That's when I resorted to the med!
     
  16. roxie60

    roxie60 Senior Member

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    Aileen Can definitely relate to your sleep (or lack of) experiences. I had all of that at various times. That is what is so frustrating, how are w suppose to function and make commitments when our bodies are all over the place in terms of dysfunction.....:cry:, I feel for ya hon, it is so aggravating. I also tried meds but they were usually not effective or added symps. It seems if I have to take a med for extended period of time I get side affects. Any meds I can take that are limited in time (like taking pain meds as needed, not regularly) I seem to manage.
     
  17. Beyond

    Beyond 10% of discount in iHerb!--> PEZ915

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    I am CT for first and GG for second... So I fall in the genetically prone to be sleep deprived :sleep: Makes sense.
     
  18. Bluebell

    Bluebell Senior Member

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    How do you fall into the sleep-deprived group? The risk alleles, according to Roxie60, are C for the first and T(A) for the second, so you only have 1 of 4 risk alleles. Is there some info I'm not looking at?

    I've tried to look at the original research study, but it is hanging my Internet Explorer and all my windows grey out when I try to read it. What I was able to catch a glimpse of was,
    "The CLOCK gene is located in position 4q12 and it contains 20 exons.348 One polymorphism in the 3′ flanking region of the CLOCK gene, a T-to-C substitution at position 3111, is known to affect mRNA stability and half-life.349 In healthy par -ticipants, the C allele was associated with a significantly greater delay in preferred timing for activity or sleep.350 In mood dis -orders, the same C variant was coupled with higher recurrence rates in patients with bipolar disorders,351 increased lifetime sleep disturbances352 and persistence of insomnia during anti-depressant therapy.353 Recently, a significant association between rs3736544 (T allele) and response and between rs3749474 (C allele) and remission has been found.354"

    What do "response" and "remission" indicate? Are we sure that those are the "risk" reactions? I am not saying they aren't, it's just that I can't see what the study is looking at, and I don't know if that's the only part of the study where these RS numbers are mentioned because my computer just doesn't want to let me look at the study!

    ---
    Beyond, I have the same alleles that you do for those 2 SNPs.
    About half of the population does (when considering the 2 SNPs individually). How could these two common SNPs indicate people who are going to have serious sleep issues? That doesn't seem reasonable to me. My circadian clock issues are not shared by a substantial percentage of the population.
    Maybe there is something I'm not aware of here (it's likely!)
     
  19. roxie60

    roxie60 Senior Member

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    I'm never totally sure about risk alleles so if someone finds info to the contrary please post. This was just my conclusion based on these studies. As always I could be wrong. Just trying to see if others with sleep distrubances have these alleles as a kind of independent sample to verify.
     
  20. Bluebell

    Bluebell Senior Member

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    The study referred to in the following sentence of the main study that we are talking about here, "Recently, a significant association between rs3736544 (T allele) and response and between rs3749474 (C allele) and remission has been found.354"

    is this study: http://www.ncbi.nlm.nih.gov/pubmed/19347611

    It is about "response to fluvoxamine treatment in Japanese major depressive disorder patients"

    What they found was:
    "...remission with fluvoxamine was also significantly associated with rs3736544."
    "Our results indicate that CLOCK genotype may be a predictor of fluvoxamine treatment response in Japanese MDD."
    "However, our sample size was small, and a replication study using larger samples may be required for conclusive results."

    I think that "remission" might mean that the patients' depression got better when taking the drug fluvoxamine?

    All this stuff is so complicated, but I don't think that we can infer from this study anything about having sleep problems in general.
     
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