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New Gene Linked to PTSD Identified

Discussion in 'Genetic Testing and SNPs' started by Waverunner, Aug 8, 2012.

  1. Waverunner

    Waverunner Senior Member

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    The 23andme equivalent should be TT for higher PTSD risk.

    (rs8042149)

    http://www.sciencedaily.com/releases/2012/08/120807132213.htm

    ScienceDaily (Aug. 7, 2012) — Investigators at Boston University School of Medicine (BUSM) and Veterans Affairs (VA) Boston Healthcare System have identified a new gene linked to post-traumatic stress disorder (PTSD). The findings, published online in Molecular Psychiatry, indicate that a gene known to play a role in protecting brain cells from the damaging effects of stress may also be involved in the development of PTSD.

    The article reports the first positive results of a genome-wide association study (GWAS) of PTSD and suggests that variations in the retinoid-related orphan receptor alpha (RORA) gene are linked to the development of PTSD.
    Mark W. Miller, PhD, associate professor at BUSM and a clinical research psychologist in the National Center for PTSD at VA Boston Healthcare System was the study's principal investigator. Mark Logue, PhD, research assistant professor at BUSM and Boston University School of Public Health and Clinton Baldwin, PhD, professor at BUSM, were co-first authors of the paper.
    PTSD is a psychiatric disorder defined by serious changes in cognitive, emotional, behavioral and psychological functioning that can occur in response to a psychologically traumatic event. Previous studies have estimated that approximately eight percent of the U.S. population will develop PTSD in their lifetime. That number is significantly greater among combat veterans where as many as one out of five suffer symptoms of the disorder.
    Previous GWAS studies have linked the RORA gene to other psychiatric conditions, including attention-deficit hyperactivity disorder, bipolar disorder, autism and depression.
    "Like PTSD, all of these conditions have been linked to alterations in brain functioning, so it is particularly interesting that one of the primary functions of RORA is to protect brain cells from the damaging effects of oxidative stress, hypoxia and inflammation," said Miller.
    Participants in the study were approximately 500 male and female veterans and their intimate partners, all of whom had experienced trauma and approximately half of whom had PTSD. The majority of the veterans had been exposed to trauma related to their military experience whereas their intimate partners had experienced trauma related to other experiences, such as sexual or physical assault, serious accidents, or the sudden death of a loved one. Each participant was interviewed by a trained clinician, and DNA was extracted from samples of their blood.
    The DNA analysis examined approximately 1.5 million genetic markers for signs of association with PTSD and revealed a highly significant association with a variant (rs8042149) in the RORA gene. The researchers then looked for evidence of replication using data from the Detroit Neighborhood Health Study where they also found a significant, though weaker, association between RORA and PTSD.
    "These results suggest that individuals with the RORA risk variant are more likely to develop PTSD following trauma exposure and point to a new avenue for research on how the brain responds to trauma," said Miller.
    This study was supported by the National Institute on Mental Health of the National Institutes of Health under award number R01 MH079806 and a grant from the Department of Veterans Affairs.
     
    merylg likes this.
  2. alex3619

    alex3619 Senior Member

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    Very interesting waverunner.
     
  3. Waverunner

    Waverunner Senior Member

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    Thanks, Alex. I'm a layman but do you think that gene therapy might be useful for CFS?
     
  4. Tito

    Tito Senior Member

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    Gene therapy? Maybe
    But I think there are real hopes to use genetic markers to identify subgroups among ME patients. IMHO this will be the turning point for us.
     
  5. Waverunner

    Waverunner Senior Member

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    Thanks for that input, Tito. Can you estimate, how much longer it takes, till we will have valid genetic markers for CFS?
     
  6. Enid

    Enid Senior Member

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    Mmm - but why at the age of healthy 62 should my genes fail me.
     
  7. Crux

    Crux Senior Member

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    Hi Waverunner;

    Thanks for the link. The term PTSD caught my mind. My recovery from it has involved a great effort. CBT was the least effective, if at all. I think it's because the therapist was too fixated on her own problems to be able to teach any sort of logic to others.

    I believe that the tendency towards PTSD is largely physiological. Some people are naturally more resilient than others, and have been able to recover from horrific episodes.

    For myself, B12, and other supplements for proper methylation, have been the very most effective for recovery. I believe that they are helping to repair my damaged DNA, nerves, as well as enabling me to use logic.

    Here's an abstract that links decreased RORA gene activity to methylation problems:

    http://www.ncbi.nlm.nih.gov/pubmed/20375269
     
  8. Firestormm

    Firestormm Guest

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    Thanks for this as I think it is interesting also.

    The way I read this (and in part I'm speculating) but it need not only be a significant stressor or single event that leads to long term effects of this gene deficiency. I would suggest that it is continuing stress that is as likely a consequence. Question is (or one of them) to what degree any symptoms and debilitation can be attributed to a faulty gene and whether PTSD can be applied to (or is part of) any/every long term neurological condition.

    I don't think that a single event is as consequential as a series of continuing events/continuing stress. There might be a trigger but this gene fault could be (speculating) what separates one person who suffers from the same event recovering and getting on with things, and another person who continues to suffer.

    Then again of course if you have something biologically wrong with you by way of an illness say something pertaining to your immune system, leaving you susceptible to infections say, then repeated insults or repeated stressors will be a determining factor also.

    I'm not sure how big this news is. I would have thought a published paper might have received some greater attention. Perhaps one will be forthcoming but it's an interesting development. Makes you think doesn't it?
     
  9. Tito

    Tito Senior Member

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    @ waverunner
    I think within the next 10 years we might be able to identify the main subgroups of people 'at risk', because there is more than our genetic makeup. The fact that for most patients, the disease starts quite abruptly gives a clue of something else too. But there must be a genetic aspect too because in clusters, no everybody became ill, just a tiny minority. I think if we can identify that predisposition factor, we might be able to trace back the culprit. For example, if it happens that only people with blood group A develop the disease then we know that we need to search around that antigen, maybe a virus with that receptor or a cascade of biochemical reactions that only happen with that antigen around. You see what I mean?
    @ enid
    Generally speaking, the later a disease start, the less likely the genetic cause and the more likely an environmental factor. But there are counter-examples. Take Huntington disease. It is related to a single gene but can start at 60 even later. It could also be the story of a gene switching off when it should stay on or vice versa.

    My feeling is that many 'traditional' paths have been explored and led to very little. So the genome might now offer an entirely new instrument to understand this illness. So far, our group is too heterogeneous, we need to classify patients more rigorously on some specific markers (and not symptoms as done in the past). If we take the example of leukemia, it is when sub groups were identified that considerable progresses were made. Nowadays survival rates for leukemia are pretty high.
     
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  10. Tito

    Tito Senior Member

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    I often think about this issue of a triggering factor followed or not by a perpetuating factor. I believe ME is a disease of the brain that affect all organs, the immune system, the hormones, etc. I think there is a possibility that we were hit once by a virus that left an injury deep in our brain that leads to all these subsequent problems WITHOUT any perpetuating factor. If we take the example of polio, the virus arrives, damages the nerves before being eradicated by the immune system and the patient remains paralysed. In our case instead of our motor abilities, it is our other neurological abilities that are left injured.
     
  11. Gestalt

    Gestalt Senior Member

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    How did you figure that out?
     
  12. Firestormm

    Firestormm Guest

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    Here's a dumb question. I know very little about genetics. You don't need to be born with a genetic defect do you? I mean it can result through something encountered in life, right? Something that could be as damaging as what is being talked about above. Need a 'back to basics' I think :)
     
  13. Gestalt

    Gestalt Senior Member

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    The genetic defects discussed here, are permanent, meaning you were born with them and can't change them and the defects exist in the DNA of every cell in your body. They are in most cases inherited from one of your parents, unless a mutation occurs somewhere in the conception process. In any case you are stuck with them for life, unless you manually go and change the DNA in every cell of your body which currently is not possible, but perhaps some day it will be.

    That being said DNA can become damaged/mutated by external factors or even internal replication factors, however this occurs on a individual cell by cell level only, and won't affect the entire genome. It can effect further cells that replicate/come from a mutated cell though. This is how cancer forms.
     
  14. Firestormm

    Firestormm Guest

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    Much obliged. Thanks Gestalt. What are your thoughts on this news? Potentially significant for PTSD and is there anything possibly in it that might apply beyond PTSD?
     
  15. Waverunner

    Waverunner Senior Member

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    http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2012113a.html

    "Examining the probability of a PTSD diagnosis by genotype indicated that subjects with relatively low levels of exposure to trauma with the high-risk (GG) genotype had a similar likelihood of developing PTSD as those from the high-exposure group but with the low-risk (AA) genotype (63% and 61%, respectively)."
     
  16. alex3619

    alex3619 Senior Member

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    Hi Waverunner, there are two issues. The first is that gene therapy only works to target defects in specific genes. A patient has to have those defective genes - so it might help some of us, but not all of us.

    The second issue is, I think (I have not researched this anything like recently), gene therapy is still not reliable. It has risks. One of the problems that sometimes occurs is that viral vectors can induce major problems in gene recipients - including cancer.

    Gene therapy on plants and microbes is dead easy. On animals, including humans, we haven't worked out the bugs.

    One of the alternatives, which I think is viable for some genes, is to supplement the gene product like a drug. This has risks too, but maybe not as much. However this may mean using genetically modified bacteria to grow the product, with all the risks of contamination that may lead to.

    The other problem is this. Just because a gene is associated with a symptom or disorder does not mean we understand the mechanism. A lot more research may need to be done. With that research in hand other treatments might be possible.

    Bye, Alex
     
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  17. peggy-sue

    peggy-sue

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    Is it at all likely that somebody with this predisposition would in future, be exempt from military employment?
     
  18. alex3619

    alex3619 Senior Member

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    Hi Gestalt, there is one exception to this that I know of. If a mutation or other error occurs during tissue differentiation in the womb, then genetic problems may only exist in a specific tissue type.

    Hmmm, I just thought of another one. While every cell with a nucleus will have a specific gene (or defective gene), in the case of the X chromosome in women this might lead to a patchwork of defects. This is because of X chomosome silencing. Basically, every cell only has one operating X chromosome. The other is silenced. This is random, though I think this happens during tissue differentiation (I do not recall the specifics). So a defective gene on the X chromosome will only be active in half the cells in the body. This might mean that some symptoms would appear in some parts of the body, and not others.

    Men only have one X chromosome and so do not have an X chromosome that is silenced.

    Bye, Alex
     
  19. alex3619

    alex3619 Senior Member

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    My guess is not, but they might reject volunteers with this problem. In times of war they probably wont care. However it might make post-war care easier to obtain, with less argument. Bye, Alex
     
  20. Steve-22

    Steve-22

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    I am TT for the rs8042149 and can't get over my Dad's death that happend 8 years ago.The memory is too vidid,it slowly destroyed my life becoming from a forever smiling,clumsy (ASD) child to a guy you can see on my profile picture,developed muscle weakness and clinical depression,lost the few friends I had.
    Dad was the person I loved the most,now he is the person I hate the most because I couldn't find any other ways to forget him other than starting to hate him.
    I don't think this is normal at all.Isn't there a treatment for this other than antidepressants,that already ruined my life? Will methylation support fix this? I can't accept this fate.
    Is there anyone who would accept it? ...

    If you google you can find ptsd causing permanent brain damage.
     

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