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Thread: Scioliosis is caused by infectious disease

  1. #61
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    More Schizophrenia stuff

    concerned dad

    bag o' schizophrenia goodies

    Link found between Tick-Borne Encephalitis and schizophrenia

    California researchers say 'flu virus in mothers can trigger schizophrenia and autism
    (Scientists may have discovered the mechanism involved)

    Schizophrenia linked to immune response in womb
    (Easy to understand chat with a scientist on the subject)

    Toxoplasma Infection Increases Risk Of Schizophrenia, Study Suggests

    Toxoplasmosis Parasite May Trigger Schizophrenia And Bipolar Disorders
    (Scientists may have discovered another mechanism)

    Schizophrenia is probably caused by many different types of damage that result in similar symptoms. Because these disorders are hard to understand they get lumped together. Maybe the brain tends to "break" in a certain kind of way.
    Last edited by Dingo; 05-05-2009 at 10:27 PM.

  2. #62
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    Narcolepsy is an autoimmune disorder

    concerned dad

    One more recent story.

    May 5, 2009 -Narcolepsy Is An Autoimmune Disorder, Stanford Researcher Says

    Mignot and his collaborators have shown for the first time that a specific immune cell is involved in the disorder-confirming experts' long-held suspicion that narcolepsy is an autoimmune disease.
    Mignot and others believe that the body's immune system plays a role in killing hypocretin-making cells, primarily because of scientific literature showing a link between narcolepsy and a variant for the human leukocyte antigen, or HLA, gene. The immune system uses HLAs to differentiate between "self" cells and foreign cells (and attacks those presented as foreign), and most autoimmune diseases are associated with variants of HLA. In recent studies, more than 90 percent of narcolepsy patients were shown to carry one such variant.
    May 4, 2009 - Immune fault 'link' to narcolepsy

    Dr Mignot said: "Narcolepsy is probably the result of a series of unfortunate events, starting with genetic predisposition, involvement of an environmental trigger such as an infection, then T-cell activation, then effects on many other arms of the immune system."
    Put simply a microbe or some other environmental agent triggers a destructive immune response in genetically susceptible people. The body destroys the neurons that produce Hypocretin and Narcolepsy sets in.

    The fact that genes may correlate with a specific illness doesn't mean much until scientists understand the mechanisms behind the disorder. The truth is that on some level genes correlate with EVERY illness. Once scientists discover the environmental trigger behind Narcolepsy we can probably vaccinate against it and put this one in the history books.
    Last edited by Dingo; 05-05-2009 at 11:32 PM.

  3. #63
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    Quote Originally Posted by Dingo View Post
    If Scoliosis is not caused by environmental damage why do you suspect that MZ twins are discordant most of the time?
    There is no good reason to suspect they are discordant most of the time.
    Sharon, mother of identical twin girls with scoliosis

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  4. #64
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    Quote Originally Posted by PNUTTRO View Post
    check the references in this paper

    Adolescent idiopathic scoliosis in twins: a population-based survey.
    Andersen MO, Thomsen K, Kyvik KO.
    Spine. 2007 Apr 15;32(8):927-30.
    PMID: 17426641 [PubMed - indexed for MEDLINE]
    I looked at the paper P referenced and extracted some sections to share. Apparently P, Dingo, and Sharon know much about the twin issue but I didn’t and in case anyone else is following along, the first paragraph below gives some background about why twin studies are important for genetics.

    Twin studies offer an unparalleled opportunity to determine the contribution of genetics to a disease because the potentially confounding effect of shared environmental factors is significantly reduced. Monozygotic twins have identical genes, while dizygotic twins like siblings share 50% of their segregating genes. Both types of twins share common environment to the same degree, having been subjected to, for example, the mother’s smoking, drinking, and nutritional habits during pregnancy. An increased proportion of double-affected monozygotic twins compared to dizygotic twins (concordance) indicates a genetic etiology of a disorder.

    I think P was referring me to the references below to show the other studies with higher concordance.

    From a review of the literature and from their own observations, Kesling and Reinker10 identified 100 sets of twins with AIS. They reported that the concordance rate, given as a simple proportion, of idiopathic scoliosis is about 0.73 in monozygotic twins and 0.36 in dizygotic twins. Inoue et al11 found concordance rates of 0.92 and 0.63 in monozygotic and dizygotic twins, respectively, in their study of 21 pairs. These concordances could be consistent with Mendelian inheritance of AIS. Both these twin studies, however, rest on case reports and hospital registers, which overrepresent concordant pairs because there is a double chance of the pair being ascertained. This type of study may overestimate concordance.

    Present Study Results

    The pair-wise concordance was 0.13 (95% CI 0.05– 0.27) for monozygotic and zero (95% CI 0–0.03) for dizygotic pairs. The proband-wise concordance was 0.25 (95% CI 0.17–0.37) for monozygotic and zero for dizygotic pairs (P _ 0.05).


    In their discussion they say

    In this population-based twin study with 11,740 complete pairs, we noted a significantly higher pairwise and proband-wise concordance for AIS in the monozygotic twins than in the dizygotic twins, and this indicates that genetic factors are important for the etiology. The concordance for monozygotic twins is far below 1 and, therefore, environment must also be important in the etiology of AIS.

    Then another paragraph with some background info for people like myself.

    Twin studies are particularly useful in distinguishing the relative contributions of genetics and environment to the cause of a disease. If genetic factors are important, concordance in monozygotic twins, who are genetically identical, will be greater than in dizygotic twins, who share the same number of segregating genes as other siblings (50% on average). If a disorder is solely genetic in origin, concordance among monozygotic twins approaches 1, and a concordance below 1 in monozygotic twins is, thus, an indication of the importance of environment for the etiology of the disease.

    They go on to say, and this is where they also talk about problems with the references P is considering that shows higher concordance


    In our opinion, and in accordance with the studies by Wynne-Davies8 and Riseborough and Wynne-Davies,9 the present study supports the assumption that there is a significant genetic component in the etiology of AIS. The risk of AIS occurring in a monozygotic twin whose other twin has the disease is, however, only 25%, and a figure substantially lower than that reported in other twin studies. The concordance reported by Kesling and Reinker10 of 0.73 in monozygotic and 0.36 in dizygotic twins was
    calculated on a total of 37 monozygotic and 31 dizygotic twin pairs. These 68 pairs were described in publications from 12 different authors, among whom Berquet23 and Fisher and De George24 contributed 43. The remaining pairs are case reports. Inoue et al11 gave concordance rates of 0.92 and 0.63 in monozygotic and dizygotic twins, respectively, in a study of 21 pairs.


    And then, seemingly in response to Sharons comments they say

    With none of the dizygotic pairs concordant in the present study, one may ask whether they have been overlooked. We do not believe that this is the case. A population- based twin cohort of more than 30,000 subjects has been screened for self-reported scoliosis, and in this cohort there was no bias toward monozygotic and concordant pairs. We have the expected proportions of dizygotic pairs in the registry,12,13 and the twins were sampled because they were twins, not because of disease. With the known prevalence of AIS,20 we can estimate that we might have missed 1 concordant pair of twins. Even if this were the case, it would not have altered either the results or the conclusions.

    They conclude with

    Our findings suggest that heredity is an etiological component in AIS. Environmental factors must also be important, and this knowledge is of potential benefit in prioritizing future research into this disease.

    I dont think this shows anyones argument is right or wrong. It is genetics and it is environment, both. I think I understand it just a little bit better now though.

    However, regarding P's comment about natural selection, your statement is, at best, oversimplified. Selective pressure does not mean an absence of sexual reproduction, just a, well, "pressure" acting over many generations.

  5. #65
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    Good work, as usual, CD. Some comments below...

    Quote Originally Posted by concerned dad View Post
    I looked at the paper P referenced and extracted some sections to share. Apparently P, Dingo, and Sharon know much about the twin issue but I didn’t and in case anyone else is following along, the first paragraph below gives some background about why twin studies are important for genetics.

    Twin studies offer an unparalleled opportunity to determine the contribution of genetics to a disease because the potentially confounding effect of shared environmental factors is significantly reduced. Monozygotic twins have identical genes, while dizygotic twins like siblings share 50% of their segregating genes. Both types of twins share common environment to the same degree, having been subjected to, for example, the mother’s smoking, drinking, and nutritional habits during pregnancy. An increased proportion of double-affected monozygotic twins compared to dizygotic twins (concordance) indicates a genetic etiology of a disorder.
    And when DZ twins have a concordance rate of zero like Dingo's pet study, that would seem to rule out a highly infectious agent at least.

    I think P was referring me to the references below to show the other studies with higher concordance.

    From a review of the literature and from their own observations, Kesling and Reinker10 identified 100 sets of twins with AIS. They reported that the concordance rate, given as a simple proportion, of idiopathic scoliosis is about 0.73 in monozygotic twins and 0.36 in dizygotic twins. Inoue et al11 found concordance rates of 0.92 and 0.63 in monozygotic and dizygotic twins, respectively, in their study of 21 pairs. These concordances could be consistent with Mendelian inheritance of AIS. Both these twin studies, however, rest on case reports and hospital registers, which overrepresent concordant pairs because there is a double chance of the pair being ascertained. This type of study may overestimate concordance.
    This study might also understate MZ vice DZ. If comments from some mothers are to be believed, even doctors don't realize that about half of all MZ twins have the same outer/inner sack configuration as all DZ twins (i.e., two outer sacks.) Apparently some doctors and many lay people think that two outer sacks means DZ twins. Wrong. Unless there is one outer sac, you cannot use number of outer sacks to determine MZ versus DZ. You have to test. And you certainly can't take the word of people as evidenced by the Olsen twins and others who can be shown to use entirely specious reasoning for their conclusion that they are not identical.

    Present Study Results

    The pair-wise concordance was 0.13 (95% CI 0.05– 0.27) for monozygotic and zero (95% CI 0–0.03) for dizygotic pairs. The proband-wise concordance was 0.25 (95% CI 0.17–0.37) for monozygotic and zero for dizygotic pairs (P _ 0.05).


    In their discussion they say

    In this population-based twin study with 11,740 complete pairs, we noted a significantly higher pairwise and proband-wise concordance for AIS in the monozygotic twins than in the dizygotic twins, and this indicates that genetic factors are important for the etiology. The concordance for monozygotic twins is far below 1 and, therefore, environment must also be important in the etiology of AIS.
    With zero concordance between DZ twins, if it is a parasite, it highly NON-infectious and likely relies on some genetic component OBLIGATELY.

    Then another paragraph with some background info for people like myself.

    Twin studies are particularly useful in distinguishing the relative contributions of genetics and environment to the cause of a disease. If genetic factors are important, concordance in monozygotic twins, who are genetically identical, will be greater than in dizygotic twins, who share the same number of segregating genes as other siblings (50% on average). If a disorder is solely genetic in origin, concordance among monozygotic twins approaches 1, and a concordance below 1 in monozygotic twins is, thus, an indication of the importance of environment for the etiology of the disease.
    This ignores things like gene copy number (and who knows what else) which may or may not be important in something like scoliosis or anything for that matter. That is, MZ twins are known to differ in gene copy number and this alone and all by itself may explain the huge discrepancies sometimes seen in curves between MZ twins like with my baby kids. And because of this huge discrepancy in curves even between MZ twins, on top of the huge underidentification of MZ twins, cases of self-reporting should be assumed to be GARBAGE IN - GARBAGE OUT until proven otherwise.


    They go on to say, and this is where they also talk about problems with the references P is considering that shows higher concordance


    In our opinion, and in accordance with the studies by Wynne-Davies8 and Riseborough and Wynne-Davies,9 the present study supports the assumption that there is a significant genetic component in the etiology of AIS. The risk of AIS occurring in a monozygotic twin whose other twin has the disease is, however, only 25%, and a figure substantially lower than that reported in other twin studies. The concordance reported by Kesling and Reinker10 of 0.73 in monozygotic and 0.36 in dizygotic twins was
    calculated on a total of 37 monozygotic and 31 dizygotic twin pairs. These 68 pairs were described in publications from 12 different authors, among whom Berquet23 and Fisher and De George24 contributed 43. The remaining pairs are case reports. Inoue et al11 gave concordance rates of 0.92 and 0.63 in monozygotic and dizygotic twins, respectively, in a study of 21 pairs.
    I'll take studies with fewer twin pairs who were KNOWN to be MZ versus DZ through testing (if that is the case with the other studies) over self reported twin status and curve status ANY DAY OF THE WEEK. The Danish Study is highly flawed in my opinion and I don't trust the data AT ALL.

    And then, seemingly in response to Sharons comments they say

    With none of the dizygotic pairs concordant in the present study, one may ask whether they have been overlooked. We do not believe that this is the case. A population- based twin cohort of more than 30,000 subjects has been screened for self-reported scoliosis, and in this cohort there was no bias toward monozygotic and concordant pairs. We have the expected proportions of dizygotic pairs in the registry,12,13 and the twins were sampled because they were twins, not because of disease. With the known prevalence of AIS,20 we can estimate that we might have missed 1 concordant pair of twins. Even if this were the case, it would not have altered either the results or the conclusions.
    They are too near the noise level to say one way or the other.
    Last edited by Pooka1; 05-06-2009 at 11:42 AM.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

  6. #66
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    I had to google concordance to better understand.
    So, for others

    Twin concordance: The odds of a second twin getting a disease if the first twin does.

    And when DZ twins have a concordance rate of zero like Dingo's pet study, that would seem to rule out a highly infectious agent at least.
    So, DZ twins have the same gene distribution as siblings while MZ twins have identical genes.
    You're saying the zero DZ concordance rules out a highly infectious agent. I suppose I would have to agree. It doesnt rule out an infectious agent, just a highly infectious agent.
    It would seem to rule out something that occured in utero also as both DZ and MZ twins would have been exposed ot he same environment.

    Apparently some doctors and many lay people think that two outer sacks means DZ twins. Wrong.
    What is a "sack" ?

    With zero concordance between DZ twins, if it is a parasite, it highly NON-infectious and likely relies on some genetic component OBLIGATELY.
    Makes sense to me. Dingo, any comments?

    This ignores things like gene copy number
    Too lazy to google, what exactly is gene copy number? Are you saying MZ twins do not have the same genes?


    cases of self-reporting should be assumed to be GARBAGE IN - GARBAGE OUT until proven otherwise.
    This kills me when you do this. You cant just throw up your hands and dismiss something because of inherent weaknesses. (going back to lack of random controls (due to ethics) in our brace study discussions).

    I'll take studies with fewer twin pairs who were KNOWN to be MZ versus DZ through testing (if that is the case with the other studies) over self reported twin status and curve status ANY DAY OF THE WEEK. The Danish Study is highly flawed in my opinion and I don't trust the data AT ALL.
    Do you think the danish twin study is flawed in general or just how it approaches scoliosis issues? It seems to me that it is a pretty oft cited study and they would have been able to determine by now if there are issues relating to the self reporting by looking at other (better studied/characterized) diseases.

  7. #67
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    And when DZ twins have a concordance rate of zero like Dingo's pet study
    I forgot to mention, this SPine paper IS Dingos pet study

  8. #68
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    One more thing

    You're saying the zero DZ concordance rules out a highly infectious agent. I suppose I would have to agree. It doesnt rule out an infectious agent, just a highly infectious agent.
    It would seem to rule out something that occured in utero also as both DZ and MZ twins would have been exposed ot he same environment.
    I dont know about this. WHy couldnt it still be a highly infectious agent but, since the DZ twins do not have identical genes, only the twin with the genetic susceptability gene gets it?

    Seems like a better argument against a highly infectious disease is the relatively low MZ concordance.

  9. #69
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    parasite

    concerned dad
    pooka1


    With zero concordance between DZ twins, if it is a parasite, it highly NON-infectious and likely relies on some genetic component OBLIGATELY.
    Low MZ and DZ concordance is strong evidence against a "genetic" or "natural biological process" explanation.

    90% of all Narcoleptics share the same gene but the disorder is triggered by an infection. Perhaps a microbe evolved a way to defeat the job this gene performs. That's how stuff works. The fact that MZ and DZ concordance are different suggests that Scoliosis might work the same way.

    The concordance for monozygotic twins is far below 1 and, therefore, environment must also be important in the etiology of AIS.
    Anyone want to take a stab at what the environmental variable might be?

    A) It's been around for thousands of years
    B) It harms and occasionally kills children
    C) Humans haven't been able to evolve an airtight defense against it
    Last edited by Dingo; 05-06-2009 at 01:44 PM.

  10. #70
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    Quote Originally Posted by Dingo View Post

    Low MZ and DZ concordance is strong evidence against a "genetic" or "natural biological process" explanation.
    I dont think what you said is correct because they said in their paper that:

    we noted a significantly higher pairwise and proband-wise concordance for AIS in the monozygotic twins than in the dizygotic twins, and this indicates that genetic factors are important for the etiology.

    A higher MZ concordance than DZ concordance suggests genetics IS important.

    You note that both MZ and DZ concordances are low, but MZ is greater than DZ which points to the importance of genetics, no?

    Dont suppose anyone ever did a twin study on narcolepsy?

    Regarding taking a stab at an environmental variable, well, looking forward to hearing what Sharon and P have to say

  11. #71
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    genetics and scoliosis

    concerned dad

    A higher MZ concordance than DZ concordance suggests genetics IS important.
    I don't mean not important at all. The fact that MZ is higher than DZ indicates some sort of genetic susceptability. But the fact that both are so low argues against a "natural" Scoliosis biology. Something is clearly going wrong or they'd be the same most of the time.

    Dont suppose anyone ever did a twin study on narcolepsy?
    Monozygotic twins with narcolepsy: preliminary report

    Narcolepsy is so rare (1 in 2000) that twin pairs are hard to come by.
    In this small sample of 12 MZ pairs 3 are concordant and 9 are discordant.
    Last edited by Dingo; 05-06-2009 at 02:24 PM.

  12. #72
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    Indoor heated swimming pools: the vulnerability of some infants to develop spinal asymmetries years later.

    funny how much wierd stuff you can find out there.

    Do parasites live in clorinated pools?

    most of the swimming pool paper can be found in this google book

    clicking on that link reveals my thought process and how one abstract comment points another in a different direction.
    I googled "fossil evidence of scoliosis" in response to Dingos comment about the environmental cause being around for 1000's of years, i wondered if it may even be millions of years. That led me to a dead end but I did come accross this bizarre swimming pool paper.

    And Dingo, I like your subliminal suggestion about Parasites when you titled your previous post (the one inviting us to take a stab at the environmental variable)

    Last edited by concerned dad; 05-06-2009 at 02:58 PM.

  13. #73
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    Quote Originally Posted by concerned dad View Post
    What is a "sack" ?
    In the womb, babes are in two sacks:

    Chorion = outer sack
    Amnion = inner sack

    All DZ twins have their own chorion and therefore their own amnion.

    About half of all MZ have their own chorion and therefore their own amnion (identical to ALL DZ twins).

    About half of MZ twins have ONE chorion and their own amnions. This is like two smaller balloons inside one big balloon. My baby kids were like this and so we know FOR A FACT they are MZ without a lick of further testing required.

    A very small percent, maybe less than one percent of MZ twins are in the same amnion and therefore in the same chorionic sack. These twins do not fair well and often hang each other in each other's cords. I think both twins are lost about half the time in these pregnancies, unfortunately. And as always, that's some fancy "intelligent" design. How people can believe their is a designer god insults the intelligence of a 6 year old.

    Too lazy to google, what exactly is gene copy number? Are you saying MZ twins do not have the same genes?
    I read a while ago about some research showing that MZ twins can have wildly different numbers of particular genes and so are not identical genetically, at least in that respect. So they have same genes but can have different numbers (repeats) of them. If I had to grasp for the most likely explanation of why my twins have wildly different curves I would guess it might be related to different copy numbers of genes which control, at least in part, the rate of curvature and the rotation at least. Those are the things that differ wildly between my girls.

    Then there are epigenetic effects that I would tend to group with "genetic" but will not because P will dope-slap me if I do so.

    Do you think the danish twin study is flawed in general or just how it approaches scoliosis issues? It seems to me that it is a pretty oft cited study and they would have been able to determine by now if there are issues relating to the self reporting by looking at other (better studied/characterized) diseases.
    I can't say about other diseases.

    I CAN say I have met more parents who denied seemingly obvious MZ status than have admitted it. And I can say my MZ twins differ wildly in curves. Together, this means that self-reports of either zigosity status or even having a curve is highly suspect to the point of it being very likely GIGO. FULL STOP
    Last edited by Pooka1; 05-06-2009 at 03:32 PM.
    Sharon, mother of identical twin girls with scoliosis

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    Quote Originally Posted by concerned dad View Post
    One more thing,

    I dont know about this. WHy couldnt it still be a highly infectious agent but, since the DZ twins do not have identical genes, only the twin with the genetic susceptability gene gets it?
    Well it is at least an argument against putting too much emphasis on environment. If it was highly infectious the concordance rate would be sky high for both MZ and DZ twins.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

  15. #75
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    Quote Originally Posted by Dingo View Post
    Anyone want to take a stab at what the environmental variable might be?

    A) It's been around for thousands of years
    B) It harms and occasionally kills children
    C) Humans haven't been able to evolve an airtight defense against it
    Laying babies on their backs of course!
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

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