Sunday, March 11, 2012

The “Sleep-duration” Gene

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The “Sleep-duration” Gene

Dr. Maggie Pearce explains the discovery and promise of a recent journal article by Allebrandt et al. According to Allebrandt et al. and their research on the ABCC9 gene in Drosophila (fruit flies), this gene is related how much sleep we need per night. Although this is a very interesting discovery, how can we be sure that the SNP in the ABCC9 gene actually causes the 5% difference in sleep duration among people? Can Allebrandt et al. declare that ABCC9 really is the cause of difference in human sleep patterns, if their experiments were done in Drosophila or does this call for more experimentation and investigation? If you could design an experiment to test this gene’s impact on sleep duration, how would it be different that Allebrandt et al.?


In another article by the BBC, expert Neil Stanley said that there are many genes associated to sleep patterns. He also said, "It's interesting to know about these genes, but in a way our genes are an irrelevance unless you were actually to obey them - but none of us do that." (http://www.bbc.co.uk/news/health-15999489)
 This seems to contradict the last paragraph of Dr. Maggie Pearce’s article that you read. Do you agree more with Dr. Pearce or Neil Stanley? Why?

20 comments:

  1. I do not think that the Allebrandt et al. study is specific enough to be accurate. Did they use an average of sleep for both work nights and free nights? Or is it just one or the other? It is not very clear the details of how the study was performed. The next step might be to look at several variables such as caffeine intake, age, gender, profession before measuring amount of sleep. These factors are so important in sleep duration that I think they need to be looked at as well. How can they know for sure that sleep is not affected by a different gene making one person more affected by caffeine than another?

    I don't believe that there is enough evidence with genetic testing in fruit flies, because although they are similar to humans, they are very different. But it is something to look into further in humans, perhaps in a larger cohort study.

    Also, a half hour of sleep is not that significant. I think that if it were a greater amount of time that they would be onto something. It just seems as if this could be a pattern that happened to show up in the study, not something that is directly linked to the ABCC9 gene.

    Finally, I think that Neil Stanley is trying to say that no matter what our genes say, we do not obey them. If we need to be awake for something early in the morning or we go out late one Saturday night, we are not listening to our genes. So although looking at the effect of ABCC9 and potassium on sleep is an interesting concept, it may not help us learn too much, other than some people need more and some need less. I feel like if we start to alter this gene things may get tricky because we all need sleep to function, whether it is four or ten hours, and altering this may be controversial.

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    1. I agree that the Allebrandt study was much too vague to make any kind of convincing argument. In the end, all I got from that article was that sleep may or may not be controlled by the ABCC9 gene. -_- Not only that, but what was considered to be the baseline for the study participants... their weekday sleep patterns or their weekend sleep patterns? I did like how the article explained what SNPs and GWASs are before talking about them; it seemed like the writer really wanted the reader to get a good idea of what was studied, even though the study barely revealed anything.

      I'm also glad she acknowledged the gross over-comparison made between fruit flies and humans. I think too many external factors dictate our sleep schedules to look too much into a gene/genes, and certainly to compare to other animals that don't have 8am classes and work at all hours of the day. Did the time of day a person slept and the # of times a person slept in a day influence the study results in any way? I still do not understand what sleep measurement was taken to be the standard.

      For sleep linked gene studies, I'm going to side with Neil Stanley and say that external factors decide my sleep patterns (or lack thereof).

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  2. While I agree with Hannah that the Allebrandt et al. study alone does not provide sufficient evidence to prove that the ABCC9 gene definitively causes sleep variation in humans, I do think that the cross sectional survey aspect of the study provides reasonable support for the hypothesis.

    A few key points to consider:
    1. The European study had a sample size of 4,251 participants. Less than the 10,000 reported by the BBC but still a significantly large population pool.
    2. It doesn't appear that age or gender were taken into consideration but these factors can influence the amount of sleep an individual needs, as noted by Dr. Pearce.
    3. The study included participants that were not required to work the next morning. This touches upon what Neil Stanley is arguing⎯if our genes provide us with a disposition to a specific and ideal amount of sleep, it's almost un-noteworthy because it has little influence on how much we actually sleep. What really determines the number of hours we sleep each night is what's around us. Whether it be work, school, or a combination of these things.

    It's fascinating that scientists have been able to isolate the ABCC9 gene with respect to sleep variation, but I think I'll side with Neil Stanley on this one. Environment overrides what our genes are telling us when it comes to sleep.

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  3. I agree with Suzann and the Neil Stanley article that our environment overrides what our genes are telling us in regards to sleep. What is demanded of us (or not demanded of us) influences our choices about sleep. Sleep is sometimes largely a choice. I think it would be interesting to explore what epigenetic changes might occur as we age and have changing lifestyles. For example, if an individual changes to a more demanding job with longer hours and earlier mornings, it might be challenging at first but that person will adjust and it becomes routine. Could this make epigenetic changes that impact generations? Referring to the question in the prompt, I think that might be an interesting topic to explore.

    Also, at the bottom of the BBC News article there was a link to an article under the "similar articles" section from 2007 called "Genes Determine Sleep Demands" http://news.bbc.co.uk/2/hi/health/6431971.stm The study had participants stay awake for 48 hours and see how the "Period 3" gene impacted sleepiness and performance on tasks in those groups. They also tested which group spent more time in slow wave sleep. They thought to apply the results to what times workers are most likely to have sleepiness-related accidents. This is just another way to apply this type of research. Also, I'm sure there are more gene variations and SNPs that are being researched in relation to sleep. Another study would be to see how these might interact or influence each other in certain combinations in individual sleep needs.

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  4. These two articles provide insight into the effects genes have on sleeping but a causal relationship cannot be determined. The study showed that humans with ABCC9 gene sleep a half hour more and fruit flies without the gene slept three hours less. The Drosophilia part of the study cannot automatically prove anything in humans. While humans and Drosophilia are similar in most genes, they are still different and these differences call for more experimentation in humans. As Suzann mentioned above, participant characteristics must be included when looking at a sleep study; for example: age, gender, race.

    I agree with Neil Stanley more in that genes are irrelevant unless we obey them. While I think the isolation of the ABCC9 gene could be beneficial for those with sleeping disorders, especially in the field of pharmacology, I do not see the benefit for most people. So what if our genes say we need an extra thirty minutes of sleep? Will this really change our daily routine? Can’t we tell when we are tired and need more sleep, without knowing whether or not we have the ABCC9 gene? The study looked at sleep habits on “free days”. But do these free days take into account whether you sleep with shades or blinds, or if you have a child or a pet that wakes you up when they do? There are so many other factors that contribute to sleep. Even if we know we should be getting more sleep, which is the case for most people, that does not mean people will change their behavior, or in Stanley’s words “obey” their genes.

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  5. Other than genes being responsible for how much sleep one needs, I also think a lot depends on one's day and one's daily activities. Some students just go to class in a day whereas others go to class, work a few hours at an internship, play a club sport at college, and attend meetings and/or do homework. I believe that the second kind of student I mentioned needs more sleep since he or she is using up much more energy during the day. As the article stated, "Other factors like age, gender and time of year can affect how many hours of sleep you need. And your health can play a big role, too." This makes sense. Before I think of genes, these are the main factors that immediately come to my mind regarding sleep.

    This new study found that people with a certain difference in a gene called ABCC9 needed about half an hour less of sleep every night. Since this is a very minimal difference, personally I do not think this can be used to account for small differences like 30 minutes of sleep without a lot more evidence. The article then goes on to state, as I just expressed concern, "Of course, just because they all share this SNP does not necessarily mean that it causes them to need less sleep. Scientists need more evidence than that." They then looked at fruit flies, since most of their genes are related to ours. Their studies on the flies also showed a possible correlation between the ABCC9 gene and sleep time. Flies and humans are still extremely different from each other though, so before I can be convinced, I would need to read many more studies on this confirming their hypothesis.

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    1. I agree with Michelle that a persons sleep pattern can depend on other factors like their daily activities.

      A 30 minute difference in sleep time to me, is not significant enough. Researchers may want to take their findings from working with fruit flies, and experiment on people enrolled in sleep studies. Maybe people will discover that in order to have the most productivity in their day, their is a specific minimum hours of sleep they need. In other words, in order to be productive and not feel tired during the day, an individual will be able to determine when they should go to bed, for instance 9pm each day.

      Those who end up needing more sleep can structure their day so that they can accomplish whatever they need to be done while leeving enough time for sleep. That way, no one should be making any excuses for sleeping in late but rather why they should be sleeping earlier.

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    2. I think it is really important, as Michelle and Elizabeth have pointed out, to consider that sleep patterns are very related to one's daily activities, job, personal habits and environment. In addition to the activities Michelle mentioned that might require a very active person to get more sleep, job and lifestyle are also important factors in considering sleep habits and needs. For example, a person who works a night shift will likely have very different sleep habits than someone who works a 9-5 job or someone else who is unemployed. Or someone who has kids and gets woken up in the middle of the night frequently is going to have different sleep patterns/needs than someone who can sleep soundly through the night without disturbances. Or even lifestyle habits like staying up late at night can affect how much sleep someone actually needs or gets. In this way, our genes may in some ways be responsible for how much sleep we need per night, but these needs can translate into differing sleep patterns and needs due to a variety of lifestyle and non-genetic related factors that affect human behavior. Perhaps the ABCC9 gene can't really account for many of the observed variations in human sleep patterns, as environment, activity level, lifestyle and personal habits may be important factors that remain unaccounted for in the genetic code.

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  6. Allebrandt et al.'s study, though certainly showing an interesting correlation, does not truly prove anything, as Neil Stanley stated at the end of his article. His last statement is one that I have been thinking in the back of my mind while we have learned about several genetic tests. It brings up an important question of free will, a question that will surely be questioned in future legal battles concerning genomics.
    We know that individuals with a genetic predisposition towards alcoholism do not necessarily develop alcoholism, that individuals with AVPR1A gene 334 do not always end up in unhappy relationships though their genetics suggest that they will. If individuals have a predisposition to require extra sleep to be optimally active, does that mean they can never be early risers? I don’t think so. But, we must also remember that there is much we do not know about our genome. Are all of our vices and relationships in fact predetermined by our unique genomes, and our limitations are merely that we do not yet know which combinations of genes produce which effect? If this is the case then how do we explain the differences between preferences of identical twins? There are a plethora of questions that this article has raised for me about free will and genomic predisposition, questions that will become more and more relevant as the medical field continues to expand in its abilities. If we learn all of the possible genetic combinations that lead to exhibited phenotypes, and genetic intervention in gametes becomes more advanced, we run the potential for being able to design our offspring, which is possibly the largest infringement upon free will that our world has yet to face.

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  7. To be sure that the ABCC9 gene actually causes the 5% difference in sleep duration among people there would definitely have to be a detailed case study formed. Because there are so man confounding factors to take into effect a set of people may have be isolated for set amount of time to measure the difference between having or not having the ABCC9 gene. Even with a case study this may not be effective because a lot of us don’t follow our genes. I personally could sleep for a very long time but with years of waking for school and daily activities, I no longer need as much sleep as I did as a young child. Another negative would be that there basing their discovery off of flies. As stated in Dr. Maggie Pearce’s article, Flies and humans are pretty different from each other so you can’t really draw too many conclusions from what is perceived to occur in flies. A huge difference would be flies having TWO sleep periods and humans having ONE every 24 hours. I definitely agree more with Neil Stanley in saying that there are so many genes associated with sleep pattern that no definite assumption can be made. Gaining more knowledge on this gene would of course be beneficial and could result in new findings but there are way too many factors to take into account. The external environment has a big impact on what we do and many times we go against our genes to adapt to the environment. A SNP in the ABCC9 gene may result in humans requiring less sleep but knowledge of having or not having this gene doesn’t help a healthy individual who may have to go against their genes anyway.

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    1. Ashley makes some really good points about these two articles. I agree that no definite assumption can really be made and that Dr. Stanley's comment is more realistic than Dr. Pearce, but there is still valuable knowledge to be taken from Dr. Pearce's article. Fruit flies are commonly used in pilot studies in order to understand human behavior, and knowledge/evidence obtained from studies as these are important. I think that the next step would be to try to move to small mammals, such as mice or other rodents to test the investigator's hypothesis on the ABCC9 gene.

      I'm a little hesitant about the study design of the sleeping study that looked at the sleeping patterns of 4,000 participants, however. The researcher's definition of "needed sleep" is too vague for my liking. It seems like the investigators just noted how much sleep each individual got each night, but that doesn't necessarily depict how much they NEED. A large percentage of people never sleep enough and wake up tired because they need to go to work, etc-- so the fact that researchers may have considered the amount of sleep that a sleep deprived person received as the amount of sleep they "needed" is not very accurate at all. This definition of "required sleep" is incomplete and will certainly skew results. I also do not feel that a difference of 30 minutes of sleep is significant enough to draw any conclusions. People oftentimes vary the number of hours they sleep day by day. So a 30 minute difference does not seem as significant as, say 1 or 2 hours.

      More research needs to be conducted because this could potentially be a great scientific discovery. But I do not feel that the evidence produced from both the fruit fly study and the human subject study is incontrovertible just yet.

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  8. Veronika SychevskayaMarch 17, 2012 at 2:30 PM

    I would like to talk about how the researchers did not mention REM sleep, a sleep cycle is 90 minutes long and according to the ABCC9 gene you only save a 30 minutes but I am confused how this would actually help people in sleeping. If someone wants to feel more rested it is less about the time they sleep and more of the sleep cycles they fully complete. I would be skeptical in trying to adjust for one gene to sleep 30 minutes less and this goes into agreeing with Neil Stanley on how there are many genes that regulate sleep and other things that just because one gene has been found to do one thing doesn't mean the environment or ourselves will be able to see the same results. People still need to get up at a certain time for work or school no matter what their genes would want them to do. I also had trouble understanding Dr. Pearce's article when they were trying to explain about how ABCC9 worked they just said it works with potassium, well yes the whole body does that's how neurons send signals, I would have liked a more detailed description on how it works, and if they don't know then I would not have added that part.

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  9. Dr. Stanley's assertion that people do not follow genetic tendencies regarding their sleep patterns is accurate and could explain some discrepancies. Studies have shown that people do not naturally follow a 24-hour cycle with one 8-hour sleep period when not prompted by environmental cues like daylight, but shift to a longer, 25-hour circadian rhythm. It's quite possible that our natural sleep behavior much more closely mimics that of the fruit flies than our artificially altered patterns do.

    Even though fruit flies are very different creatures than humans, the conservation of genetic information throughout the evolutionary process would indicate we do share many similarities in our genetic code (though theirs is, of course, much smaller). Such a basic function as sleep, coded for in Drosophila DNA, likely has the same basis as human sleep genes and could provide insight for researchers.

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  10. The findings from Allebrandt et al.’s study can only suggest an association between the ABCC9 gene and nighttime sleep duration in humans. As Dr. Pearce notes, that people with the SNP in the ABCC9 slept a half-hour less than people without it does not prove that the SNP causes the difference in sleep duration among people. Allebrandt et al.’s experiment with Drosophila (the fruit fly) suggests that the ABCC9 gene homologue in fruit flies affects how much fruit flies sleep at night. The findings from this experiment provide further evidence to suggest a role of the ABCC9 gene in human sleep duration, since fruit flies and humans have similarities in their genes. (Although, again, it is not sufficient evidence to prove that the SNP in the ABCC9 gene causes people to need less sleep.) As Dr. Pearce points out, we have to be careful in translating the results from the fruit fly experiment because humans and fruit flies are still very different from one another. Furthermore, Allebrandt et al. turned down the expression of the ABCC9 gene in fruit flies, and this is not the same as having a change in the DNA sequence of the ABCC9 gene.

    I am curious about the methods that Allebrandt et al. used in their study. Dr. Pearce said that the researchers were careful to determine how long people sleep on weekdays versus free days, but I am curious as to how they determined how much sleep they needed each night. And how were subjects designated into categories based on the increments of sleep needed? (How did subjects neatly fit into either groups of needing either 7.5 versus 8 hours of sleep?) Furthermore, as others have mentioned, many other factors (such as age, gender, and circadian rhythm) affect how much sleep we need each night. What external factors did Allebrandt et al. take into consideration?

    More research is needed to determine the impact of the ABCC9 gene in human sleep duration. I am assuming that Allebrandt et al. used adult study subjects, so I am wondering what would happen if they studied children. Would the results hold true for children (that is, would children with the SNP in the ABCC9 gene need less sleep than children without it)? I think it would be especially interesting to study the ABCC9 gene in infants, who probably have fewer extraneous factors affecting their sleep.

    Dr. Pearce says that it is relevant to know about the ABCC9 gene because we might be able to use information about this gene to come up with ways of helping people with sleep problems. I am curious about what types of sleep problems Dr. Pearce is referring to. When I think of sleep problems, I think of problems like insomnia (trouble falling/staying asleep), sleep apnea, and sleepwalking, where it seems that factors other than a possible sleep duration gene contribute to the problem.

    On the other hand, Neil Stanley says that genes are, in a way, irrelevant because we do not obey them. I, like the other students, have to agree with Neil Stanley. While I do not doubt that genes affect how much sleep we need, I think that for most people, external factors are the predominant factors in determining how much they actually sleep at night. People set their sleep schedules around school, work, appointments, and other obligations. In addition, other factors such as caffeine intake, alcohol, diet, and stress level can affect how much people actually sleep.

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  11. Any lay person is likely to find Pearce's study promising granted that it is published in Standford University's School of Medicine webpage. However, as others have noted as well, the method, hypothesis, conclusions, etc., aren't as specific as one would hope. Thus, I definitely agree others & Neil Stanley that the environment overrides any influence that our genes may have with our sleep patterns. I think a lot of how long a person sleeps is "taught" in one or another by a sense of repetition. Scheduling oneself to sleep at a specific time and then wake up at a particular time is bound to influence one's "biological clock" to adapt to the current routine, regardless of one's genes. This leaves me to be skeptical of the extent to which our genes can effect how much or how little we sleep.

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  12. I agree with Min. I think the environment has a massive impact on how and when we sleep. Actually, I think that the environment may even outweigh any effects our genes have on our sleep. Even if you are gentically prone to fall asleep a lot more easily or for a longer period of time or spend a longer amount of your sleep time in REM cycle, the environment can completely change that. Say you're living next to an airport, or a highway, you're bound to be woken up by noisy vehicles many time during the night. And napping during the day could also be a challenege considering plane's flying schedules are pretty constant.
    I also agree with Anna in the fact that a lot more research needs to be done on the ABCC9 gene. I really liked her idea of looking into how this gene effects children. Maybe we could also look at babies and eldery people to see if there are any significant differences.
    Overall, I have to agree with Neil Stanley because I too believe that genes are somewhat irrelevant when it comes to sleep cyles and how much sleep we need. As college students, we're constantly faced with many interfering factors that affect our sleep patterns (midterms, finals, exams in general, lab reports, classes, jobs, and then there are those three day weekends...) So honestly, I think that one's environment has a much larger impact on when and for how long we lay down to sleep.
    - Caroline Booth

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  13. I also feel as though Pearce's study is unreliable. Any study on sleep is going to have multiple variables due to environmental factors associated with sleep patterns. That being said, I agree with Neil Stanley because there are so many things that can affect a person's sleep habits. Work, family, stress, diet, and a variety of other aspects of daily life can all impact a person's sleep patterns. People can develop a routine that is effective depending on their schedules. Furthermore, I believe that there must be more research done regarding the ABCC9 gene to establish if it is in fact related to sleep habits.

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  14. I too agree with Neil Stanley. I find it interesting that scientists are searching for genetic answers to sleep patterns. However, I believe environmental factors, especially at our age as Caroline mentioned, are the driving factors of sleep time and duration. I do not think Dr. Pearce's study has much clinical utility as a half hour difference in sleep duration, in my opinion, does not seem to be a monumental finding, especially when it does not consider the environmental factors. I do think that these studies could be the groundwork for additional sleep studies that will perhaps produce more clinically useful findings.

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    1. I don’t think we can be completely be sure that the SNP in the ABCC9 gene actually causes the 5% difference in sleep duration among people. Just because in the study they all share this SNP does not necessarily mean that it causes them to need less sleep. We definitely need more evidence and even though scientist did further research with the fruit flies that isn’t enough for me personally to agree with the causation. Even though flies and humans have related genes, they are still pretty different from each other. And having a small DNA difference in your ABCC9 gene is probably very different from turning down the dSur gene in flies. Nevertheless we can’t 100% be sure that the conclusion is correct but isn’t most of science just a guess anyway…maybe there is some connection and after a few trial and errors this could lead to something substantial.
      In addition, as Hannah said I would like to see how they picked the people to do the study and how they were able to compare the differences in lifestyle, eating patterns..etc. And I know every minute of sleep counts but I also agree with Hannah and Nina that 30 minutes isn’t a long amount of time and I wonder if the study added up the minutes and rounded them up to 30 or was it even less.
      If I were to design an experiment I would do the test on monkeys since they are pretty close to humans genetically.
      I also think that Neil Stanley is trying to say that we don’t listen to our genes because there are certain things that we shouldn’t be doing but we do it anyway, like when we eat too much or drink too much, smoke, stay up too late..etc. There are so many other factors involved and they are affecting our genes too. So although looking at the effect of ABCC9 and potassium on sleep is an interesting and could lead to a lot of new discoveries, if we “listened” to our genes we could probably do more on our own and without as much money. So regardless of what they discover, as Michelle and Elizabeth have pointed out as well, outside factors such as activities, personal habits, an environment affect sleeping patterns.
      In addition I also think that Anna brought up a great point about Dr. Pearce saying that it is relevant to know about the ABCC9 gene because we might be able to use information about this gene to come up with ways of helping people with sleep problems. I would also like to know what the sleeping conditions were because I feel like sometimes there are other ways for treating for those issues and other things that contribute to them as well.
      Overall…when it comes to sleep studies I am a little hesitant especially when it comes to treatment because I feel like if there is a drug that could allow you to sleep less…it might become popular on college campuses and lead to an issue as Adderall has.

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  15. I agree more with Neil Stanley because he seems to see genes as only one factor of many that affect sleep and therefore does not think we should place a huge emphasis on genes. Although Dr. Pearce acknowledges these other factors, he seems to imply that the ABCC9 gene could greatly impact our need of sleep. Since there are so many factors involved, the affect genes have would only be a very small percent of the overall. Even if altering the gene allowed you to get less sleep, factors such as anxiety might still cause you to need more sleep. If you have a very high level of anxiety and it severely impacts how much sleep you need it might be so significant that a small change in your ABCC9 gene wouldn't even make a difference.
    Also, some factors might even over-ride any changes that could be caused from altering the ABCC9 gene. For example, medications such as beta blockers that affect sleep might still influence the amount of sleep needed regardless of a change in your ABCC9 genes.

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