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Dingo
04-25-2009, 12:42 AM
Everyone knows that Scoliosis is a common side effect of Polio infection.

Do other infections cause Scoliosis? You bet.

Fish scoliosis triggered by parasite (http://www.cababstractsplus.org/abstracts/Abstract.aspx?AcNo=20053000841)

Horse Scoliosis triggered by parasite (http://www.cababstractsplus.org/abstracts/Abstract.aspx?AcNo=20043001514)

Alpaca scoliosis triggered by parasite (http://www.ncbi.nlm.nih.gov/pubmed/16910858)

Goat scoliosis triggered by parasite (http://www.ncbi.nlm.nih.gov/pubmed/1253609)

Google Search: parasite scoliosis (http://www.google.com/search?hl=en&q=parasite+scoliosis)

It bears repeating that if one identical twin has Scoliosis the other has it just 13% of the time (http://www.scoliosis.org/forum/showthread.php?t=8480). This strongly suggests that in most cases Scoliosis is triggered by something in the environment.

13% pairwise concordance is roughly equivelant to what's found in Multiple Sclerosis which is triggered by Epstein Barr virus. (http://www.theaustralian.news.com.au/story/0,25197,24678376-5006786,00.html) Epstein Barr is more famously known as the cause of Mono "the kissing disease".

In this landmark Scoliosis study (http://pico.sssup.it/files/allegati/2004_1469.pdf) all 58 children in the sample had the same type of nervous system disorder. Although they share the same disorder nobody is suggesting that they share the same gene or gene cluster. Every child in the sample had severe scoliosis that progressed to fusion and yet 2/3rds did not have a single 1st, 2nd or 3rd degree relative with any type of spinal deformity.

rtremb
04-25-2009, 03:09 AM
My husband and I think there is a connection between our daughter's scoliosis, her very serious case of chicken pox with cellulitis and her subsequent serious case of PANDAS (Paediatric AutoImmune Neuropsychiatric Disorder Associated with Strep).

PANDAS causes the immune system to attack itself (see quote below) and we have wondered if it has caused weakness in the muscles around her spine.

The proposed theory of the pathophysiology of PANDAS is an immune-mediated model of molecular mimicry, the same mechanism suggested for rheumatic fever. After exposure to antigens on the surface of Group A beta-hemolytic streptococcus during a streptococcal infection, the body develops antibodies to combat the bacteria. In susceptible individuals, the antigenic area of the bacteria is similar enough to endogenous host tissue, causing a cross-reaction of the antibody to the host; therefore, formulating an autoimmune attack on it’s own tissue. This causes a local immune reaction to the targeted tissue; i.e. – brain, joints, heart valves. In rheumatic fever, this causes heart valve damage, arthritis, and abnormal neurological movements termed Sydenham’s chorea. In PANDAS the antibodies are thought to cross-react with neuronal tissue of the CNS, in particular the basal ganglia of the brain, which is responsible for movement and behavior – resulting in tics and/or OCD.

PANDAS research is still in its early stages since this condition was only really recognized a few years ago. The doctors keep finding out new things about this condition. Maybe a connection will be found between PANDAS and scoliosis.

My husband has talked to a couple of orthopaedic doctors about this possible connection but they tell us we would need to talk to a rheumatologist about this. Of course, we don't have access to a rheumatologist now since Esme is no longer symptomatic with the PANDAS.

Anyway, this is just a hunch on our part. Maybe one day a connection will be made between PANDAS and scoliosis especially in those who are predisposed by other factors like having other scoliotic family members.

It is hard to accept "idiopathic" as the explanation for scoliosis. It seems only logically there must be a reason/cause as yet undiscovered for the "idiopathic" cases.

Ruth

Pooka1
04-25-2009, 11:44 AM
That's an interesting post though I wonder if those animal models will ever map to humans.

In re this "old chestnut," :)



It bears repeating that if one identical twin has Scoliosis the other has it just 13% of the time (http://www.scoliosis.org/forum/showthread.php?t=8480). This strongly suggests that in most cases Scoliosis is triggered by something in the environment.

I have been thinking about this. The big question in my mind is how/why did other ID twin studies report much higher concordance compared to this one?

The question has to be asked why this one study disagrees with most/all of the others.

That is more interesting to me than the actual results.

I think there is almost certainly something in the methodology that will explain the difference. I would hope the full article addresses what they think is the reason for having results that have not been duplicated.

I don't know if this figures in this but I certainly hope they didn't just take people's word on the matter of identical versus fraternal. I have noticed in real life there is a tendency to not admit identical twinning when it is seemingly obvious. A famous example is the Olsen twins who publicly claim they are not identical when it is beyond obvious they are identical. They substituted for each other on that show for years and they still appear far more identical than my own daughters who I know for a fact are identical (one chorion which is dispositive for identical twinning).

The reasons given by people for thinking their kids are not identical are uniformly specious (two chorions, different freckle patterns, different hair swirl patterns, different heights/weights, etc.). My kids differ in most of these things and more biologically significant ones (one is allergic to sulfa drugs and the other is not) and yet are still identical.

Now I don't think sulfa drug allergy is in the same category as scoliosis. I am just saying if one report differs from the bulk of the other reports, that one report needs further scrutiny. They may be right and all the other wrong but we have to know why. I'm skeptical until a reasonable explanation is on offer. They don't have to prove it at this point, it just has to be reasonable. But if later reports don't corroborate it, it's going to be some methodological problem.

Dingo
04-25-2009, 03:21 PM
Ruth

It is hard to accept "idiopathic" as the explanation for scoliosis. It seems only logically there must be a reason/cause as yet undiscovered for the "idiopathic" cases.

I agree, all illness has a cause. Idiopathic means that we don't know. When you hear a scientist say, "This particular disorder is caused by a complicated interaction between genes and the environment" that's fancy science talk for "I have no idea".

I don't know if PANDAS is related to Scoliosis. Perhaps a compromised immune system leaves a child vulnerable to both.

Dingo
04-25-2009, 03:40 PM
Pooka1

The Dutch twin study was credible because it used a large, representative sample from a twin registry. Work like that makes small studies with questionable samples obsolete.

If the Dutch study is replicated using another twin registry it will cement the original find. Unless some shenanigans were going on in Denmark I doubt the numbers will be vastly different in other European countries. Alain Moreau's study of children with severe Scoliosis found that 2/3rds didn't have a single relative with spinal deformities. That's consistent with the Dutch twin study.

13% is a low concordance rate but to be honest even 50% would not be considered particularly high. Tuberculosis has an identical twin concordence rate of around 50% and it's an infectious disease caused entirely by bacteria.

Dingo
04-25-2009, 03:50 PM
YouTube: Gold fish with Scoliosis (http://www.youtube.com/watch?v=rQ4c_UVcRCQ)

I'm not sure if this is Scoliosis but it could be. One of the commenters mentioned Whirling Disease (http://en.wikipedia.org/wiki/Myxobolus_cerebralis). Either way it's probably a parasite because in fish both Scoliosis and Whirling Disease are caused by parasites.

Pooka1
04-25-2009, 06:03 PM
Pooka1

The Dutch twin study was credible because it used a large, representative sample from a twin registry. Work like that makes small studies with questionable samples obsolete.

Not if they are relying on self-reporting for identical versus fraternal. I can tell you from experience the number of identical twin pairs will be EXTREMELY underestimated and therefore both groups will have misindentified individuals.

Dingo
04-26-2009, 08:56 PM
Pooka1

I have no obvious reason to think that the Dutch researchers made mistakes but it's always possible.

For arguments sake let's say they misidentified some fraternal and identical twins.

Identical twins were 13% concordant
Fraternal twins were 0% concordant

No matter how those numbers shift between the two groups this study suggests that in most cases heredity plays very little role in Scoliosis.

Pooka1
04-26-2009, 09:01 PM
Pooka1

I have no obvious reason to think that the Dutch researchers made mistakes but it's always possible.

For arguments sake let's say they misidentified some fraternal and identical twins.

Identical twins were 13% concordant
Fraternal twins were 0% concordant

No matter how those numbers shift between the two groups this study suggests that heredity plays very little role in Scoliosis.

Yes I see that but what is their explanation for why they have such outlier results? There is some radically different point in their methodology vice all the other reports.

Can you think of some way that all the other reports coincidentally arrived at an erroneously high concordance? The burden is on the outlier report even though the other reports may have had few subjects because they all generally agree).

For example, they are relying on self reporting for the incidence of scoliosis, no? If true, is that really adequate? I can see how it would result in extreme under-reporting.

Pooka1
04-26-2009, 09:03 PM
And another thing... if it is environment/parasites and not genes then why the zero concordance between fraternal twins? Twins generally do the same thing at the same time for the first several years of their life in my experience.

Zero concordance makes no sense.

The likelihood is extremely high that there is some methodological problem in that paper.

Pooka1
04-26-2009, 09:05 PM
Pooka1

I have no obvious reason to think that the Dutch researchers made mistakes but it's always possible.

Nobody has any reason to think the bulk of the researchers producing all these articles made mistakes. And yet a majority of published research results are false.

Dingo
04-26-2009, 09:14 PM
Pooka1

Yes I see that but what is their explanation for why they have such outlier results? There is some radically different point in their methodology vice all the other reports.

What we need is another large, twin registry study from another country. Who knows, this research might be in process right now.

And another thing... if it is environment/parasites and not genes then why the zero concordance between fraternal twins?

There might be 100 reasons for this. I'm not really sure.

Dingo
04-26-2009, 09:21 PM
Pooka1

There are probably a lot of adults walking around with undiagnosed 10 to 20 degree curves. But you can safely bet that most people with a 30 degree curve or greater are aware of it.

My guess is that people with moderate to severe Scoliosis made up the bulk of the respondents in the Dutch study. I would also guess that this group suffers from the strongest genetic contribution to the disease.

(time warp: this is a response to your next post)

Pooka1
04-26-2009, 09:22 PM
Pooka1

Yes I see that but what is their explanation for why they have such outlier results? There is some radically different point in their methodology vice all the other reports.

What we need is another large, twin registry study from another country. Who knows, this research might be in process right now.

And another thing... if it is environment/parasites and not genes then why the zero concordance between fraternal twins?

There might be 100 reasons for this. I'm not really sure.

Here's a big red flag about these results...

RESULTS: A subgroup of 220 subjects considered to have AIS was identified, thus giving a prevalence of 1.05%.

This is one half to one third of the incidence in the general population as I understand it and is certainly an artifact of the self reporting. As with my identical twins, one was an obvious surgical candidate and the other's case can scarcely be noticed except by those who know what to look for. I suggest the incidence of scoliosis in both twins, even identical pairs, in the twin study is highly under-reported (due to lay self-reporting) and this skews the results away from the bulk of those in the rest of the literature.

Just a thought. An explanation is required.

Pooka1
04-26-2009, 09:27 PM
Pooka1

There are probably a lot of adults walking around with undiagnosed 10 to 20 degree curves. But you can safely bet that most people with a 30 degree curve or greater are aware of it.

Completely disagree. My one daughter's scoliosis was unnoticeable and had no symptoms at ~ 30* (because of lack of rotation).


My guess is that people with moderate to severe Scoliosis made up the bulk of the respondents in the Dutch study.

Yes and people with moderate to severe scoliosis are the minority. That backs up their low incidence compared to the widely accepted figure of 2-3% IIRC.

If they had bone fide medical case histories I bet the concordance would approach that or the other published studies.

Dingo
04-26-2009, 09:32 PM
If they had bone fide medical case histories I bet the concordance would approach that or the other published studies.

It's possible but I doubt it. In Moreua's study 2/3rds of children with severe scoliosis didn't have a single 1st, 2nd or 3rd degree relative with a spinal deformity. Most of the time Scoliosis appears to come out of nowhere.

I guess we'll have to wait for another large study to get absolute confirmation.

Pooka1
04-26-2009, 09:57 PM
If they had bone fide medical case histories I bet the concordance would approach that or the other published studies.

It's possible but I doubt it. In Moreua's study 2/3rds of children with severe scoliosis didn't have a single 1st, 2nd or 3rd degree relative with a spinal deformity. Most of the time Scoliosis appears to come out of nowhere.

I guess we'll have to wait for another study.

Again, the majority of people have small or moderate curves and likely wouldn't know if they had scoliosis. And identical twins can have radically different curves as I have pointed out.

Not sure why that article is publishable. Self reporting in this area is GIGO.

Karen Ocker
04-27-2009, 10:03 AM
It's possible but I doubt it. In Moreua's study 2/3rds of children with severe scoliosis didn't have a single 1st, 2nd or 3rd degree relative with a spinal deformity. Most of the time Scoliosis appears to come out of nowhere. Dingo

I aways wonder about this because: was the question about whether the children were biological/adopted asked? Also, with so many divorces and remarriages, was the true genetic history really found. Moreua's study, as you quoted, assumes the true parentage was known. Some persons were never told they were adopted. With so much immigration, does one really know whether forbearers in foreign lands had scoliosis ?-before modern X-ray? This would weaken a study's validity don't you think?

My 2 children are adopted. When my son has his children they were worrying about them being born with scoliosis!!! My scoliosis began ~ age 10.

Dingo
04-27-2009, 12:33 PM
Karen Ocker

I'm not sure how Moreau did his study. You are right, it's certainly possible that adoption, remarriage and other factors could weaken that finding. However it's just as likely that a child with Scoliosis could be adopted IN to a family as OUT. I'm not sure if the 2/3rds would change enormously in either direction.

My guess is that Moreau would have thought about this before he looked into heredity but I can't know for sure. My personal belief is that on average research methods and study results get better over time.

BTW, although twin concordance is just 13% that doesn't mean that every case of Scoliosis is caused by environment. There certainly could be people with purely genetic forms of Scoliosis. And of course it's possible that like Polio there are no true genetic forms of Scoliosis. I guess we'll find out someday.

Pooka1
04-27-2009, 03:48 PM
The underlying assumption in this study is that the difference between concordance in identical twins and fraternal twins can isolate genetics.

Given that identical twins are known to differ at least in gene copy number, and if copy number controls (in part at least) development or severity of scoliosis, then the entire premise of all twin studied comparing identical and fraternal is flawed unless they specifically determine gene copy number or rule it out as a factor.

Lots of "if-thens" but this is a possible explanation for why some bone fide identical twins have radially different curves in my opinion. In other words, although scoliosis may be controlled largely by genetics, it would appear to be environment if they didn't look at gene copy number and if gene copy number matters.

It's things like this that make most published research results false... unknown, unidentified factors that really matter to the bottom line conclusions.

Dingo
04-27-2009, 10:28 PM
Pooka1

The underlying assumption in this study is that the difference between concordance in identical twins and fraternal twins can isolate genetics.

That's the goal. Twin studies are just one tool that give scientists a general idea about what might be going on. It helps them know how to bet. The Dutch study tells me that it's safe to bet on environment. I could be wrong but I doubt it.

Pooka1
04-28-2009, 06:48 AM
If genetic effects are indistinguishable in the study design from environmental effects then twin studies are worthless. FULL STOP

Pooka1
04-28-2009, 07:01 AM
Pnuttro is posting to this thread and I suspect we are all going to get spanked a bit for being overly expansive in our conjecture...

PNUTTRO
04-28-2009, 07:09 AM
The Dutch study tells me that it's safe to bet on environment. I could be wrong but I doubt it.

I am going to go out on a limb and tell you that you are still wrong.

An infection theory should involve communities of people. Not just families, but schools and social organization. If you said that there are populations in a geographical area that got scoliosis, I would be more inclined to agree that there is a pathogen involved. Or if there was some immunological evidence.

Scoliosis is a symptom of various disorders, infectious, genetic and environmental. You can't say that a pathogen causes scoliosis simply because other pathogen infections exhibit a similar outcome.

A correlation is not causation.


And if you respond with the same evidence that you have posted earlier, you will not convince me to change my mind.

PNUTTRO
04-28-2009, 07:12 AM
Pnuttro is posting to this thread and I suspect we are all going to get spanked a bit for being overly expansive in our conjecture...

I love it!:)

Pooka1
04-28-2009, 07:16 AM
I honestly thought this little "party" was over when I saw you replying.

It's practically a spectacle to see lay folks opining at length about this stuff, no? :D

Dingo
04-28-2009, 09:59 AM
PNUTTRO


An infection theory should involve communities of people. Not just families, but schools and social organization. If you said that there are populations in a geographical area that got scoliosis, I would be more inclined to agree that there is a pathogen involved. Or if there was some immunological evidence.

There is a difference between an outbreak disease like Polio or the Plague and the kind of microbe that might cause Scoliosis.

For instance Type 1 Diabetes is caused by the common Enterovirus (http://www.sciencedaily.com/releases/2009/03/090305141639.htm). It does appear to hit some areas of the world harder (http://www.citeulike.org/user/joepickrell/article/1048812) than others but without modern research techniques this wouldn't be obvious. Almost everyone is hit by Enterovirus but only the genetically susceptible get Type 1 Diabetes.

There is mounting evidence that brain cancer is caused by Cytomegalovirus (http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2008/10/06/MNJ8135E2I.1.DTL&type=health). 4 out of 5 people are infected with Cytomegalovirus so it doesn't make an outbreak obvious.

Another good example might be Multiple Sclerosis which appears to be triggered by Epstein Barr Virus (http://www.theaustralian.news.com.au/story/0,25197,24678376-5006786,00.html). Almost every person is infected with Epstein Barr but only a few people suffer from MS.

All of these diseases are triggered by infection but it's not obvious because almost everyone is infected. More confounding is the fact that symptoms can be delayed by years or even a decade or more.

A scoliosis microbe might enter the body, cause a few cold symptoms and knock out something important. The body's response to Enterovirus takes about a year to knock out a child's B Cells so this wouldn't necessarily happen overnight. Only years later does a parent notice that her child's spine is growing crooked.

If it's true that every child with AIS has a specific type of nervous system disorder (http://pico.sssup.it/files/allegati/2004_1469.pdf) it makes sense that Scoliosis might work something like Type 1 Diabetes. If they don't share the same gene(s) why else would they share the same nervous system disfunction? An infection that damages a specific part of the CNS makes the most sense to me. Throughout history nothing has taken out more children than infections. The 2nd place killer/damager is probably 10,000 fold less prolific.

PNUTTRO
04-28-2009, 12:32 PM
Ok. So its the same argument. Other diseases are caused by viruses so scoliosis must be caused by a virus too. Do you have any data for scoliosis?

Immunological studies tell us that these specific pathogens exist is the people with certain disorders. Is there any study that says that any pathogen exists in patients with scoliosis with a high regularity?

This is still correlation and not causation. Even the other diseases that you cite here are not definitively caused by those pathogens. The literature is littered with conflicting opinions.


Regarding glioma report (I know it has nothing to do with scoliosis. Emphasis added by me.)

Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma.
Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, Sampson JH.

Duke University Medical Center, Division of Neurosurgery, Department of Surgery,Durham, NC 27710, USA. d.mitchell@duke.edu

Human cytomegalovirus (HCMV) has been described to be associated with several human malignancies, though the frequency of detection remains controversial. It is unclear whether HCMV plays an active role in malignant tumor progression or becomes reactivated under pathologic conditions that result in chronic inflammation or immunosuppression.

Dingo
04-28-2009, 07:35 PM
PNUTTRO


Ok. So its the same argument. Other diseases are caused by viruses so scoliosis must be caused by a virus too. Do you have any data for scoliosis?

In humans scoliosis can be a side effect of Polio infection. I listed 4 animals in which Scoliosis is caused by Parasites. I only looked for a few minutes on google, there might be dozens of other examples. Do you know of any animals where Scoliosis is triggered by heredity?

In spite of this I don't believe scientists are looking for an infectious cause of Scoliosis. But like Autism researchers I'm sure they will eventually shift to environment. How else can you explain the existance of a common, worldwide, childhood CNS disorder? That sounds like Diabetes to me. Depending on where you look MZ twin concordance for Type 1 Diabetes varies from 20% to 40% or so. Scoliosis came in at 13% which is eye poppingly low. Even 50% with a low DZ rate isn't that high. I'm pretty comfortable that it's environment. Like I said before I might be wrong, but I doubt it.

PNUTTRO
04-28-2009, 09:16 PM
Spine. 2009 Jan 15;34(2):E94-100.
PMID: 19139660

Postgrad Med J. 2008 Sep;84(995):498-501.
PMID: 18940951

Spine. 2008 Sep 15;33(20):2199-203.
PMID: 18794762

Spine. 2007 Nov 15;32(24):2700-2.
PMID: 18007247

J Med Genet. 2008 Feb;45(2):87-92. Epub 2007 Oct 11.
PMID: 17932119

Dingo. Since you insist on repeating yourself, so will I. Scoliosis is an outcome, like a symptom perhaps. Think of it as a runny nose. It is an outcome that lets you know that you are sick, but wait maybe its just allergies, or you choked on your fish stick or you have spent the last 6 hours crying your eyes out.

I can't say what causes your runny nose any more than you can tell me what causes scoliosis and neither does anyone else--otherwise, they would drop the I from AIS.

Dingo
04-28-2009, 09:28 PM
PNUTTRO

You are correct, the "I" means that the trigger is presently unknown.

We have a fair disagreement, there is no reason to get testy.

You believe that Scoliosis is heredity and I believe it's environment which probably means infection. Let's give this some time and see how the research plays out.

LindaRacine
05-02-2009, 10:24 PM
Estrogen receptor polymorphysm, estrogen content and idipopathic scolisosis in human: A possible genetic linkage.
Esposito T, Uccello R, Caliendo R, Di Martino GF, Carnevale UA, Cuomo S, Ronca D, Varriale B.

Lab. of Molecular Genetics, Department of Experimental Medicine, Faculty of Medicine and Surgery, Second University of Naples, Via Costantinopoli, 16 80138, Naples, Italy.

Idiopathic Scoliosis (IS) is a largely diffused disease in human population but its pathogenesis is still unknown. There is a relationship between scoliotic phenotype and the patient age, since in the early stage the pathology shows a ratio of 50% between male and female teenagers. During puberty the sex ratio is 8,4/1 (female/male), suggesting a sex-conditioned manifestation of the disease. Genetic inheritance of idiopathic scoliosis is still unclear although some authors claim for its X-linked dominant inheritance. There is large agreement in considering the IS as a sex-conditioned disease, in terms of steroid content and their receptor activity, although no evidence have been found yet. The blood content of 17beta-estradiol in teenagers with IS shows lower levels than teenagers of the same age without IS. Also testosterone and progesterone content are lower in IS girls with respect to control girls. Furthermore, we extracted DNA from white blood cells of IS patients and their relatives until the third generation in order to examine estrogen receptor alpha polymorphisms, considering this tool a plausible molecular marker for IS prognosis. In this respect, we identified four polymorphisms in the exons encoding for the steroid binding domain and two other in the trans-activation domain. Our results show a clear relationship with clinical manifestation of IS.

Dingo
05-02-2009, 11:00 PM
LindaRacine


Results. The frequency of CC genotype of the exon ØK (in reality 5′ UTR OK-1)was significantly higher in patients than that in controls (P < 0.05). The C alleles appeared to be overrepresented in patients compared with controls (P < 0.05). Furthermore, the frequencies of CC genotypes in female patients whose height was ≥160 cm and Cobb angle was ≥30° were higher than those whose height was <160 cm and Cobb angle was <30° (P < 0.05).

Conclusion. The sites of the exon ØK polymorphisms of estrogen receptor β gene may be associated with a susceptibility of AIS. Furthermore, the sites of the exon ØK polymorphism may be associated with the height and the curve severity of patients.

It's certainly possible that scientists have discovered a susceptability gene for Scoliosis. In theory these genes could exist for every disease regardless of the cause.

However, I should note that nearly all of these are false positives.

Exhibit A
Analysis finds many genes tied to cancer don’t raise risk of getting it (http://www.msnbc.msn.com/id/28438895/)


They found that, out of 240 associations between a specific mutation and a cancer, only two genes involved in DNA repair and tied to lung cancer — XRCC1 and ERCC2 — turned out to be strong candidates for such a link.

Exhibit B
Gene-Hunters Find Hope and Hurdles in Schizophrenia Studies (http://www.nytimes.com/2008/07/31/health/research/31gene.html)


The search for common variants in schizophrenia, however, has not been very successful so far, though not for want of trying. There have been more than a thousand studies, implicating 3,608 genetic variants.

But when all the data are pooled, only 24 of those variants turn out to be statistically significant, according to an analysis in the current issue of Nature Genetics by a group led by Dr. Lars Bertram of Massachusetts General Hospital.

I should also note that infectious disease is heavily influenced by susceptability genes.

Disease 1 Gene
Gene Discovered For Type 1 Diabetes In Children (http://www.sciencedaily.com/releases/2007/07/070716133001.htm)


Pediatrics researchers at The Children's Hospital of Philadelphia and McGill University in Montreal have identified a gene variant that raises a child's risk for type 1 diabetes, formerly called juvenile diabetes.

Disease 1 Trigger
Study suggests that Type 1 Diabetes is triggered by common Enterovirus (http://www.sciencedaily.com/releases/2009/03/090305141639.htm)


It is accepted that children who develop type 1 diabetes inherit a genetic susceptibility to the disease, but studies of identical twins have shown that when one twin has the disease, the other twin will only have approximately a 40 per cent chance of developing diabetes – suggesting that factors additional to inheritance are also involved.


It has revealed that more than 60 per cent of the organs contained evidence of enteroviral infection of the beta cells. By contrast, infected beta cells were hardly ever seen in tissue samples from 50 children without the condition.

Disease 2 Gene
Leprosy Susceptibility Genes Identified (http://www.innovations-report.com/html/reports/medicine_health/report-25126.html)


An international research team lead by scientists from the Research Institute of the McGill University Health Centre (MUHC) discovered that small changes in certain genes, the Parkin 2 gene and its neighbor, PACRG, result in an increased susceptibility to leprosy.

Disease 2 Trigger
Leprosy (http://en.wikipedia.org/wiki/Leprosy) is caused by a bacteria called Mycobacterium lepromatosis. Today it is easily cured with antibiotics.

Dingo
05-02-2009, 11:39 PM
LindaRacine

Like Scoliosis many diseases hit one sex harder than the other. There is probably a different explanation for each disease.

The mystery of MS and its prevalence in Canada (http://www.cbc.ca/health/story/2008/09/18/f-multiple-sclerosis.html)


Canada has one of the highest rates of multiple sclerosis in the world, according to an international survey.


Canadian women are more than three times more likely to get multiple sclerosis than men, according to a major study published in November 2006. Among those born in the 1930s, about two women contracted MS for every one man, at a ratio of 1.9 to 1. For those born in the 1980s, the incidence has grown to exceed 3.2 cases for every one case among men.

Glandular fever link offers hope of vaccine for MS (http://www.theaustralian.news.com.au/story/0,25197,24678376-5006786,00.html)


A team from the University of Queensland has found the immune systems of people with MS are less effective at killing off EBV-infected cells. The weaker this ability, the younger the age at which MS tends to strike.

The findings add weight to theories that EBV plays a role in triggering MS. Previous studies have shown that people who have never been infected with EBV do not develop MS, and a study last year found the brains of MS patients had abnormally high numbers of EBV-infected cells.

concerned dad
05-05-2009, 03:44 PM
Honestly, I am not trying to stir the pot or create disharmony in the village but I dont know exactly where everyone stands on this matter.

Dingo makes a compelling case and I think I know where he stands and why.
I am not sure where Pnuttro stands.

Am I correct to assume that you both agree that scoliosis is not a single gene genetic disease?
I'm pretty sure you have both said that.

And, if that is the case, you both believe that SOME environmental factor has to come into play. Is that a true statement on the level of your agreement?

Dingo thinks it highly likely that it is infectious disease and P thinks it is something else in the environment.

I guess I'm confused because DIngo said to P above


You believe that Scoliosis is heredity and I believe it's environment

And I dont think I saw P say it was totally heredity. Would P say it could be an infectious disease but the evidence is not compelling enough? Or does P say, no way, the evidence points to 100% genetic?

Dingo
05-05-2009, 05:03 PM
concerned dad


Am I correct to assume that you both agree that scoliosis is not a single gene genetic disease?

And, if that is the case, you both believe that SOME environmental factor has to come into play. Is that a true statement on the level of your agreement?

In my opinion the evidence strongly suggests that genes may play some unknown role but heredity is not responsible for most cases of Scoliosis. The Danish twin study clearly indicates that in all likelihood Scoliosis is triggered by environmental input.

Environmental input = Environmental damage

The only environmental hazard that I can think of that has been around for thousands of years is a microbe. Although not proven it appears that Scoliosis is caused by pinpoint damage to the central nervous system (http://pico.sssup.it/files/allegati/2004_1469.pdf). That sounds a lot like Type 1 Diabetes (http://www.sciencedaily.com/releases/2009/03/090305141639.htm) and is another potential indicator of infection. How else could millions of children share the same nervous system disorder if they don't share the same gene?

I think I'm barely ahead of the curve on this one. It won't be long until scientists consider scoliosis an environmentally caused disease and not long after that an infectious disease.

PNUTTRO
05-05-2009, 05:11 PM
And I dont think I saw P say it was totally heredity. Would P say it could be an infectious disease but the evidence is not compelling enough? Or does P say, no way, the evidence points to 100% genetic?


P says that there is ZERO evidence of a pathogen cause for scoliosis. I believe that the causes are complex and that genetics has something to do with it. I also believe that one of the environmental factors is hormones, but I have ZERO evidence for that so I won't say that it IS A CAUSE.

Dingo's "compelling case", as I understand it, is that scoliosis is not entirely genetics, so it must be a pathogen. I disagree.

Dingo
05-05-2009, 05:24 PM
PNUTTRO


I believe that the causes are complex and that genetics has something to do with it. I also believe that one of the environmental factors is hormones, but I have ZERO evidence for that so I won't say that it IS A CAUSE.

If Scoliosis was triggered by normal hormone levels or some other natural, healthy phenomenon wouldn't you expect identical twin concordance to be a lot higher than 13%? I'm not saying that disqualifies your hypothesis but wouldn't you expect high MZ concordance?

If Scoliosis was triggered by abnormal hormone levels it would mean that people with Scoliosis were ill and we'd need to find the cause of that illness.

Pooka1
05-05-2009, 05:33 PM
PNUTTRO



If Scoliosis was triggered by normal hormone levels or some other natural, healthy phenomenon wouldn't you expect MZ twin concordance to be a lot higher than 13%? I'm not saying that disqualifies your hypothesis but wouldn't you expect high MZ concordance?

Why do you keep citing one study that has radically different conclusions that the majority of papers on this that say the concordance is much higher?

It makes no sense whatsoever to believe the one aberrant result and not the great run of other results that tend to agree. Does that mean it is definitely wrong? No. But it is likely aberrant for some good reason not related to the actual facts. That's the way science tends to work... different method - maybe different results. It's why we have papers just comparing methods that are highly publishable and valuable, at least in my field.

The most likely explanation for the outlier report that you cite is that they used a different approach and may also be GIGO (self reporting plus the known large differences in curves between MZ twins). You have no reason to think this one report is right and all the others that have a higher concordance are wrong OTHER THAN it fits your pet hypothesis. And that is a very bad way to conduct thought, not to mention science.

Can you make an argument here that doesn't rest obligately on one aberrant report?

Dingo
05-05-2009, 05:43 PM
pooka1


Can you make an argument here that doesn't rest obligately on one aberrant report?

I happen to believe that the Danish twin study is probably the most accurate. However even if concordance was 5 times higher my opinion would be the same. MZ concordance for Leprosy is 60% and it's caused by infectious disease.

Pooka1
05-05-2009, 05:48 PM
pooka1
I happen to believe that the Danish twin study is probably the most accurate.

Why? Based on what?

In my field, one aberrant report usually traces to a different method. We know this one aberrant report used questionable methods so that is the likely explanation of the aberrant results, not that hey alone are on to a more correct explanation.


However even if concordance was 5 times higher my opinion would be the same. MZ concordance for Leprosy is 60% and it's caused by infectious disease.

That elegantly shows the extreme limitations in using twin studies to sort out genetic vice environment, the same limitations that should guide your view of that study.

Dingo
05-05-2009, 05:54 PM
Pooka1


Why? Based on what?

The Danish twin study used the Danish twin's registry (http://www.demografie.de/cgi-bin/publications/paper.plx?l=en&t=&pubid=1299&personalid=3&listtype=-98) as it's sample. To me that gives it credibility.


The Danish Twin Registry is the oldest national twin register in the world, initiated in 1954 by ascertainment of twins born from 1870 to 1910. During a number of studies birth cohorts have been added to the register, and by the recent addition of birth cohorts from 1931 to 1952 the Registry now comprizes 127 birth cohorts of twins from 1870 to 1996, with a total of more than 65,000 twin pairs included. In all cohorts the ascertainment has been population-based and independent of the traits studied, although different procedures of ascertainment have been employed. In the oldest cohorts only twin pairs with both twins surviving to age 6 have been included while from 1931 all ascertained twins are included. The completeness of the ascertainment after adjustment for infant mortality is high, with approximately 90% ascertained up to 1968, and complete ascertainment of all liveborn twin pairs since 1968. The Danish Twin Registry is used as a source for large studies on genetic influence on aging and age-related health problems, normal variation in clinical parameters associated with the metabolic syndrome and cardiovascular diseases, and clinical studies of specific diseases. The combination of survey data with data obtained by linkage to national health related registers enables follow-up studies both of the general twin population and of twins from clinical studies.

Pooka1
05-05-2009, 05:56 PM
Pooka1



The Danish twin study used the Danish twin's registry (http://www.demografie.de/cgi-bin/publications/paper.plx?l=en&t=&pubid=1299&personalid=3&listtype=-98) as it's sample. To me that gives it credibility.

Do you understand my criticisms of that study? Do you dismiss every one of them? I haven't seen any argument you made against them.

Dingo
05-05-2009, 05:59 PM
Pooka1

Twin studies aren't designed to explain how an illness works. However they do provide an important data point that gives scientists an idea where they should focus.

Pooka1
05-05-2009, 06:01 PM
Pooka1

Twin studies aren't designed to explain how an illness works. However they do provide an important data point that gives scientists an idea where they should focus.

It's obvious why these twins studies are not suited for focusing future work in this area. The leprosy results alone and all by themselves show that.

concerned dad
05-05-2009, 06:31 PM
Why do you keep citing one study that has radically different conclusions that the majority of papers on this that say the concordance is much higher?



Sharon, do you have references for the other twin studies? Perhaps you posted them already but I cant seem to find them (and I understand your argument that it doesnt matter anyway - but still, it would be good to see them)

Pooka1
05-05-2009, 06:33 PM
Sharon, do you have references for the other twin studies? Perhaps you posted them already but I cant seem to find them (and I understand your argument that it doesnt matter anyway - but still, it would be good to see them)

I cribbed that comment from P. :D

concerned dad
05-05-2009, 06:40 PM
As long as you dont crib this one

P said: Natural selection doesn't get rid of scoliosis because it does not kill the individual before reproducing. The only way that a scoliosis gene would not transmit is if the curve made people so hideously ugly that no one would ever have sex with them.

Pooka1
05-05-2009, 06:47 PM
Yeah I think P was being a touch irrationally exuberant in that particular response to Dingo.

Dingo
05-05-2009, 07:02 PM
concerned dad


Natural selection doesn't get rid of scoliosis because it does not kill the individual before reproducing. The only way that a scoliosis gene would not transmit is if the curve made people so hideously ugly that no one would ever have sex with them.

If natural selection was that weak we'd still be monkeys. ;)

Pooka1
05-05-2009, 07:15 PM
If natural selection was that weak we'd still be monkeys. ;)

:D

But please don't taunt the ignorant (i.e., young earth creationists)... humans did not descend from monkeys... rather humans and other primates including monkeys have a common ancestor.

There is enough ignorance from that quarter already; No need to add to it.

Dingo
05-05-2009, 07:20 PM
Pooka1


humans did not descend from monkeys... rather humans and other primates including monkeys have a common ancestor.

I don't know exactly what humans evolved from, only that it was hairy and ate bananas. :)

Pooka1
05-05-2009, 07:22 PM
Pooka1



I don't know exactly what humans evolved from, only that it was hairy and ate bananas. :)

It wasn't monkeys. Again, the creationists have enough nonsense in their heads. We need to help them start making sense.

concerned dad
05-05-2009, 07:49 PM
I have to agree with Pnuttro when she says

A correlation is not causation.

but while digging through some stuff, I came across the following which I think Dingo will be interested in

JAMA paper (http://jama.ama-assn.org/cgi/content/full/301/3/324)
where they mention another study that says:

The results of the study by Brown et al14 revealed a dramatic 7-fold increase in the risk of schizophrenia among the offspring of women who were exposed to influenza during their first trimester of pregnancy.

And, if you google schizophrenia and genetics there are loads of hits suggesting a genetic component. Yet these guys find a seven fold increase if mom had the flu in the first trimester, hmmmmmmm

PNUTTRO
05-05-2009, 07:51 PM
If Scoliosis was triggered by abnormal hormone levels it would mean that people with Scoliosis were ill and we'd need to find the cause of that illness.

I said "I believe", I have no data. That is why I never said that it is a cause. And I said nothing about abnormal hormone levels.

PNUTTRO
05-05-2009, 08:00 PM
Sharon, do you have references for the other twin studies? Perhaps you posted them already but I cant seem to find them (and I understand your argument that it doesnt matter anyway - but still, it would be good to see them)

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]

PNUTTRO
05-05-2009, 08:02 PM
As long as you dont crib this one

Last I checked, genes are transmitted sexually. Unless you are a bacteria, virus or clone.

Pooka1
05-05-2009, 09:44 PM
And by the way...

Even if it has been shown in other animal models that scoliosis can result from a parasite, it doesn't mean it works that way in humans. Certain animal models are known to differ in certain ways from humans in plenty of respects and for known reasons.

For example, you can't give certain human antibiotics to guinea pigs.

Also, horses have a condition that is essentially Type 2 diabetes or Metabolic syndrome or both but it has a different biology if I am remembering correctly. Horses are vegetarians and humans are omnivores.

Even other primate models may not be informative on scoliosis in humans.

So citing those studies on scoliosis in other species, even if shown to be correct, is not necessarily going to advance the understanding of scoliosis in humans.

Dingo
05-05-2009, 09:46 PM
concerned dad


And, if you google schizophrenia and genetics there are loads of hits suggesting a genetic component. Yet these guys find a seven fold increase if mom had the flu in the first trimester, hmmmmmmm

Yep, and it's even more painfully obvious than that.

Children born in cities are roughly twice as likely to suffer from Schizophrenia (http://www.schizophrenia.com/prevention/country.html).

Season of birth is also a risk factor for Schizophrenia (http://www.nytimes.com/1999/02/25/us/study-shows-role-of-time-and-place-of-birth-in-schizophrenia.html?sec=health&&n=Top%2fReference%2fTimes%20Topics%2fOrganizations %2fN%2fNew%20England%20Journal%20of%20Medicine).

Schizophrenia hits around 1% of the population (http://www.schizophrenia.com/szfacts.htm). (natural selection?)

Depending on the study Schizophrenia concordance is all over the place (http://www.google.com/search?hl=en&q=schizophrenia+MZ+concordance) but it's not 100%.

These are all huge red flags that Schizophrenia is not typically a "genetic" disease.

Fortunately progress is finally being made.

June 2008 - Schizophrenia Susceptibility Genes Directly Implicated in the Life Cycles of Pathogens: Cytomegalovirus, Influenza, Herpes simplex, Rubella, and Toxoplasma gondii (http://schizophreniabulletin.oxfordjournals.org/cgi/content/abstract/sbn054)

Within a decade or two we'll have vaccines against most or all of these. I am cautiously optimistic that the rates of Schizophrenia and many other mental illnesses will drop off dramatically in future generations.

Dingo
05-05-2009, 09:58 PM
PNUTTRO


I said "I believe", I have no data. That is why I never said that it is a cause. And I said nothing about abnormal hormone levels.

I realize that you can't prove this one way or the other but you must have a reason to suspect hormones or other natural phenomenon. I have no direct evidence that a pathogen causes Scoliosis but I have several logical reasons to suspect that one does.

If Scoliosis is not caused by environmental damage why do you suspect that MZ twins are discordant most of the time?

Dingo
05-05-2009, 11:24 PM
concerned dad

bag o' schizophrenia goodies

Link found between Tick-Borne Encephalitis and schizophrenia (http://www.thelocal.se/9013/20071106/)

California researchers say 'flu virus in mothers can trigger schizophrenia and autism (http://www.autismconnect.org/news.asp?section=00010001&itemtype=news&id=6252)
(Scientists may have discovered the mechanism involved)

Schizophrenia linked to immune response in womb (http://www.abc.net.au/worldtoday/content/2007/s1979483.htm)
(Easy to understand chat with a scientist on the subject)

Toxoplasma Infection Increases Risk Of Schizophrenia, Study Suggests (http://www.sciencedaily.com/releases/2008/01/080116123517.htm)

Toxoplasmosis Parasite May Trigger Schizophrenia And Bipolar Disorders (http://www.sciencedaily.com/releases/2009/03/090311085151.htm)
(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.

Dingo
05-06-2009, 12:10 AM
concerned dad

One more recent story.

May 5, 2009 -Narcolepsy Is An Autoimmune Disorder, Stanford Researcher Says (http://www.medicalnewstoday.com/articles/148718.php)


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 (http://news.bbc.co.uk/2/hi/health/8025662.stm)


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 (http://www.usmedicine.com/article.cfm?articleID=234&issueID=29) 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.

Pooka1
05-06-2009, 06:55 AM
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.

concerned dad
05-06-2009, 11:01 AM
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.

Pooka1
05-06-2009, 12:22 PM
Good work, as usual, CD. Some comments below...


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.

concerned dad
05-06-2009, 01:17 PM
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. :D 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.

concerned dad
05-06-2009, 01:18 PM
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

concerned dad
05-06-2009, 01:22 PM
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.

Dingo
05-06-2009, 02:24 PM
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

concerned dad
05-06-2009, 02:53 PM
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

Dingo
05-06-2009, 03:21 PM
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 (http://www.websciences.org/cftemplate/NAPS/archives/indiv.cfm?ID=19960266)

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.

concerned dad
05-06-2009, 03:25 PM
Indoor heated swimming pools: the vulnerability of some infants to develop spinal asymmetries years later. (http://www.ncbi.nlm.nih.gov/pubmed/17108419)

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 (http://books.google.com/books?id=fhho8MlA6b8C&pg=PA389&lpg=PA389&dq=fossil+evidence+of+scoliosis&source=bl&ots=_WdpfCB1EF&sig=pF4jykekJ5ZivNqN-LXzC9uOzco&hl=en&ei=7N8BSp7jFJPAM_7P0eQH&sa=X&oi=book_result&ct=result&resnum=1#PPA151,M1)

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)

;)

Pooka1
05-06-2009, 04:02 PM
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. :D


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

Pooka1
05-06-2009, 04:05 PM
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.

Pooka1
05-06-2009, 04:05 PM
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!

Pooka1
05-06-2009, 04:07 PM
But the fact that both are so low argues against a "natural" Scoliosis biology.

One aberrant study says it's low.

Therefore it isn't low.

concerned dad
05-06-2009, 04:54 PM
Well, if I understand this correctly, unless the concordance were 1 (or darn close to it) there is an environental contribution.

Can we agree on that?

None of the studies says it is close to 1.

So the "abberance" of this study just goes to the degree of environmental influence. Not the need for the presence of an environmental influence.

(And I think we all know where you stand on the creationist issue. I know you feel you cant affirm it enough, but I suspect you're just preaching to the choir here and potentially offending those who feel otherwise - just my 2 cents on that :D)

Dingo
05-06-2009, 05:04 PM
concerned dad

First of all AWESOME FIND on the the pool study and Scoliosis. WOW!


Do parasites live in clorinated pools?

Yep.

Occurrence of enteroviruses in community swimming pools. (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1619862)


Municipal swimming pools and wading pools were examined for the presence of human enteric viruses using a portable virus concentrator at the site to concentrate viruses from 100-gallon to 500-gallon samples. Ten of 14 samples contained viruses; three of these were positive for virus in the presence of residual free chlorine. Enteroviruses were isolated from two pools which exceeded the 0.4 ppm free residual chlorine standard. This study appears to be supportive of recent evidence that indicates a higher incidence of enterovirus infection among bathers. All seven wading pool samples contained virus. Coxsackieviruses B3 and B4, poliovirus 1, and echovirus 7 were isolated. Total coliform bacteria were not adequate indicators of the presence of virus, as six of the samples were positive for virus but negative for coliforms. Total plate counts appeared to provide a better indication of the sanitary quality of the pool water, but viruses could still be detected in samples that met currently recommended bacterial levels. It is possible that swimming and wading pools may serve as a means of transmission of enteroviral disease, especially in children, during summer months.

Not only can Enterovirus live in Chlorinated water but scientists have strong evidence that it is the trigger for Type 1 Diabetes (http://www.sciencedaily.com/releases/2009/03/090305141639.htm).

Olympic swimmer Gary Hall Jr. (http://www.diabeteshealth.com/read/2004/09/01/3988/gary-hall-jr-/) was diagnosed with Type 1 Diabetes at around the age of 25. It's extremely rare for someone that old to come down with Type 1 however he spent countless hours in pools.

Dingo
05-06-2009, 05:10 PM
concerned dad


Well, if I understand this correctly, unless the concordance were 1 (or darn close to it) there is an environental contribution.

Can we agree on that?

Yes.
Even if concordance was 80% that doesn't mean Scoliosis is 80% genetic. It means that Scoliosis is SOME genetic and SOME environment.

Regardless of the ratio it's important that we determine what the environmental input is. That's the part we can do something about.

Pooka1
05-06-2009, 05:36 PM
Well, if I understand this correctly, unless the concordance were 1 (or darn close to it) there is an environmental contribution.

Can we agree on that?

Not necessarily. Then we look to flaws in the study design.


None of the studies says it is close to 1.

So the "aberrance" of this study just goes to the degree of environmental influence. Not the need for the presence of an environmental influence.


Possibly.


(And I think we all know where you stand on the creationist issue. I know you feel you cant affirm it enough, but I suspect you're just preaching to the choir here and potentially offending those who feel otherwise - just my 2 cents on that :D)

I would not cry if young earth creationists left ALL public fora, whether through being offended or whatever. They have shown their inability or unwillingness to handle or accept scientific evidence and so are not really useful for discussing any remotely scientific/medical topic in my opinion. They have shown a callous disregard for intellectual honesty which is arguably the entire game.

Perhaps constant reminders will help them start making sense. Or perhaps they will leave public fora on rational issues. Six on one hand, half a dozen on the other.

I am not saying kick them out. I AM saying they need to start making sense if they want to be taken seriously on ANY scientific/medical matter or anything that requires intellectual honesty.

Dingo
05-06-2009, 05:39 PM
Observations on idiopathic scoliosis aetiology and natural history in Jamaica - abstract (http://bases.bireme.br/cgi-bin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&src=google&base=MedCarib&lang=p&nextAction=lnk&exprSearch=5672&indexSearch=ID)


In 1953, the Orthopaedic Department at the University of the West Indies opened. Over the next five years, careful records were kept of the diagnosis of every patient seen in the Clinics. Amongst the findings was the observation that the idiopathic form of scoliosis appeared to be uncommon. There was a strong impression that the incidence of scoliosis was altering. From the second half of 1956, records of every patient with scoliosis from whatever cause have been kept. Only cases of severity great enough to attend an Orthopaedic Clinic and found to have a curve measuring over 10 degrees have been included. These records show that scoliosis has been an unusual condition from at least 1920 when our earliest case was reported as having developed. The condition continued to be unusal up to 1963. Then the whole position began to change. The records of the dates of presentation of new cases showed that there was a sudden increase after 1960 so that these patients became a major clinical problem. The increase in frequency rose rapidly till 1982. Then began a downturn in the number of cases which have continued. This has been in spite of a continuing annual population increase of 1.5 per cent and a steady 50 per cent of the population remaining under 15 years of age. Over the thirty-two years of this study, the general pattern of idiopathic scoliosis seen elsewhere has been found. In addition to the idiopathic group, there were almost 10 per cent due to some obvious cause. The infantile and juvenile types were seen only seldom. It was found that the idiopathic scoliosis patient was consistently above the average height for her age group and that the normal growth spurt appeared earlier in the idiopathic group than in other children. Thus, in Jamaica, there has been almost an epidemic of idiopathic scoliosis which started around 1963 and began to fall off after 1982. The increase in both the heights of these patients and their metacarpal indices suggests that something may have stimulated growth (AU)

Evidently the Scoliosis gene spread like an epidemic between 1963 and 1982. After that natural selection stepped in and it began to die out. Flu genes do the same thing year after year. Right now the Swine flu gene is spreading through Mexico. :)

Pooka1
05-06-2009, 05:39 PM
Olympic swimmer Gary Hall Jr. (http://www.diabeteshealth.com/read/2004/09/01/3988/gary-hall-jr-/) was diagnosed with Type 1 Diabetes at around the age of 25. It's extremely rare for someone that old to come down with Type 1 however he spent countless hours in pools.

I personally know two people diagnosed with Type 1 at the age of 30 (my brother and my post doc adviser).

Can't be that rare.

And neither spent inordinate amounts of time in pools. In the case of my brother, about the same as I spent in pools and I don't have it.

concerned dad
05-06-2009, 05:58 PM
I personally know two people diagnosed with Type 1 at the age of 30 (my brother and my post doc adviser).

Can't be that rare.


I cant resist playing along ....

You say it cant be that rare, Well, maybe you just know a lot more people than the average Joe and indeed it is rare.
:D

Reminds me (strangly enough) of the old line

"I've finally realized the common thread in all my disfunctional relationships is...... ME"

Dingo, interesting Jamaica paper.

Also, you say

Regardless of the ratio it's important that we determine what the environmental input is. That's the part we can do something about.

I dunno. Maybe we can do something about the genetic part too.
I happen to own a chunk of stock in a company working on what may be a cure for DMD. The company stock symbol is AVII and you can google it to find info about a currently ongoing clinical trial that we hope will show some real promise in curing this genetic disease. I have to admit, I dont fully understand the science but it at least "sounds" exciting. (This is NOT a stock tip!!!!! I have lost money on this stock and could very well loose much more)

Pooka1
05-06-2009, 06:05 PM
I cant resist playing along ....

You say it cant be that rare, Well, maybe you just know a lot more people than the average Joe and indeed it is rare.
:D

NOT! I am a hermetic recluse compared to most folks. I have few friends by choice. I like my research that requires that I'm alone in the field or out with one or a few people and I like doing bench chemistry where I'm in a lab alone and they throw food under the door. Overall, I prefer to ride my horse, alone or with an instructor helping me hone my riding skills. :D


Reminds me (strangly enough) of the old line

"I've finally realized the common thread in all my disfunctional relationships is...... ME"

:D Six on one hand, half a dozen on the other. The point is to do interesting research and maximize my saddle time.

concerned dad
05-06-2009, 06:09 PM
And Dingo, I set you up earlier


Do parasites live in clorinated pools?


Yep.

Even though I cant spell clorinated, I do know that nasty stuff can survive in pools
;)

But about your Jamaica study, I wonder if anyone looked at the incidence of scoliosis in remote populations. I've spent a lot of time in the Amazon Jungle for work and recently wondered about the occurence of scoliosis in some of the tribal peoples there. (although so many of them now are wearing Adidas t-shirts, so much for "remote")

Dingo
05-06-2009, 06:10 PM
concerned dad


Dingo, interesting Jamaica paper.

Like Schizophrenia I believe that all of the Scoliosis clues point towards infection in both humans and animals.


I've spent a lot of time in the Amazon Jungle for work and recently wondered about the occurence of scoliosis in some of the tribal peoples there. (although so many of them now are wearing Adidas t-shirts, so much for "remote")


The answer to that question might tell us a lot. Scoliosis might be really common in some tribes and virtually nonexistent in others.

concerned dad
05-07-2009, 01:31 PM
P is probably too busy or annoyed to chime in so I had to reread some old posts to try to understand the difference of opinion.


P said => The article that I referenced in this thread was a very good genetic study that, I think, has a simple take home message. A person's risk of acquiring scoliosis is determined more by one's environment rather than genetics.

So, this study is both DIngo's "pet study" and one that P thinks is good also.



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

Sharon doesnt think much of it because of the self reporting issue. I did a search and didnt see any mention of that as a drawback to the Danish Twin Study. The registry has been used for many many more studies than scoliosis. Perhaps I didnt look hard enough.

Apparently the difference of opinion goes to the infectious disease thing. Everyone agrees there is an environmental component to scoliosis.

Both Dingo and P believe the environmental component is stronger than the genetic component. (not sure where Sharon stands on that).

DIngo thinks it is likely an infectious disease and backs his theory up with similar afflictions.

P says correlation is not causation but doesnt really offer any theories about what may be involved.

OK, maybe I'm being gullable, but I think infectious diseases deserve a closer look.

(and just to let Sharon and Dingo know, I deleted the thread about SIDS and infantile scoliosis because discussing it publicly might do more harm than good)

Pooka1
05-07-2009, 06:24 PM
P is probably too busy or annoyed to chime in so I had to reread some old posts to try to understand the difference of opinion.

I think the dope-slapping cannot be far off... :D


Sharon doesnt think much of it because of the self reporting issue. I did a search and didnt see any mention of that as a drawback to the Danish Twin Study. The registry has been used for many many more studies than scoliosis. Perhaps I didnt look hard enough.

There would be no reason to suspect the huge under-reporting of MZ twins. There is no way the authors could know it absent walking around for several years with twins and meeting other parents of twins who appear scarcely sane on the zigosity of the kids.

When I realized it was happening, I couldn't explain it and certainly couldn't have predicted it. Many folks are laboring under a BOATLOAD of false notions about how different kids can be and still be MZ. Most parents of putative MZ twins (i.e., twins I would bet $1,000 of my money are MZ like the Olsen twins) are simply WRONG in their reasons for denying their kids are MZ. I mean the Olsen twins sound ridiculous when they deny they are identical and give their "reasons." There seems to also be some psychological resistance to the notion of MZ versus DZ twins but I can't prove that.

And since we know MZ twins can have radically different curves, it is possible the scoliosis incidence hasn't been (self) reported correctly either.


Apparently the difference of opinion goes to the infectious disease thing. Everyone agrees there is an environmental component to scoliosis.

Both Dingo and P believe the environmental component is stronger than the genetic component. (not sure where Sharon stands on that).

I think it is still a great unknown at this point and that genetic differences like gene copy number need to be ruled out before constructing a dichotomy like genes VERSUS environment.

In short, there is too much that is unknown at this point to have a rational, educated opinion on the matter in my (hopefully!) rational, lay opinion.


DIngo thinks it is likely an infectious disease and backs his theory up with similar afflictions.

P says correlation is not causation but doesnt really offer any theories about what may be involved.

OK, maybe I'm being gullible, but I think infectious diseases deserve a closer look.

Yes certainly but Dingo is claiming this is the most likely scenario at this point. The evidence doesn't support that for scoliosis.

concerned dad
05-07-2009, 08:28 PM
Yes certainly but Dingo is claiming this is the most likely scenario at this point. The evidence doesn't support that for scoliosis.

It seems like the most likely scenario because there are no other scenarios offered.

What about Occams Razor: Of two equivalent theories or explanations, all other things being equal, the simpler one is to be preferred.

Pooka1
05-07-2009, 10:14 PM
Okay. So is gene copy number simpler or more complex than a parasitic infection as causing/controlling the onset and degree of curvature in scoliosis?

And whatever is simplest is NOT going to entail cAMP in my opinion. :)

Pooka1
05-08-2009, 07:26 AM
Let's just see where this goes, shall we?

Zigosity Concordance

Entirely genetic and is dominant:
MZ 100%
DZ 100%

Entirely genetic and recessive:
MZ 0% or 100%
DZ 0% or 12.5%

Entirely environmental:
MZ 0% - 100% and not expected to be different from DZ
DZ 0% - 100% and not expected to be different from MZ

Complex - environmental trigger coupled with recessive genetic susceptibility
MZ higher than for DZ most but not all the time (because of the 0% above)
DZ lower than for MZ most but not all the time (because of the 0% above)

Complex - environmental trigger coupled with dominant genetic susceptibility
MZ 0% - 100%
DZ 0% - 100%

Controlled entirely by gene copy number
MZ 0% - 100%
DZ 0% - 100%

Now I am likely off on some of these numbers but it seems to me the power of these MZ/DZ twin studies is over-estimated and is only useful in a minority of situations. Only two of the above scenarios would be illuminated by twins studies. (None by self-reported twins studies.) And we don't know for sure which those are because we don't know what causes scoliosis.

Pooka1
05-08-2009, 04:10 PM
1. See if the ratio of MZ to DZ twins is in line with what we know about the general population.

Until recently when IVF and such became more prevalent, the incidence of DZ and MZ was known and known to be fairly steady. IIRC, it was about 2/3 DZ and 1/3 MZ (I should check that). The Danish twins study should be vetted to see if that ratio is close to what it should be. Of course now this ratio is all over the place and likely not steady.

2. Check that the incidence of scoliosis is about the same as in the general population. In the case of the Danish study, it is LOW by half to two-thirds. That signals a problem of under-reporting scoliosis in the study population. Because even MZ twins can differ greatly in their curves, this would seem to compromise the results per se.

Dingo
05-16-2009, 11:13 AM
Remember when scientists thought that high blood pressure was caused by an indecipherably complex interaction between heredity and lifestyle?

Maybe not.

Viral infection may trigger high blood pressure (http://www.ajc.com/health/content/shared-auto/healthnews/blpr/627039.html)


FRIDAY, May 15 (HealthDay News) -- A hidden viral infection that most adults harbor could be a cause of high blood pressure, animal studies indicate.

Mice infected with cytomegalovirus (CMV) were more likely to develop not only high blood pressure but also the hardening of the arteries called atherosclerosis, according to a report in the May 15 issue of PLoS Pathogens by researchers at Beth Israel Deaconess Hospital in Boston.

"This could be of immense importance," said lead researcher Dr. Clyde Crumpacker, a professor of medicine at Harvard Medical School and an investigator in the Division of Infectious Diseases at Beth Israel Deaconess. "The implication for the human population is that antiviral therapy or a vaccine could be an intervention for high blood pressure."


Blood vessel problems related to CMV infection were first noted in heart transplant recipients, Crumpacker said. Those who were CMV-positive were more likely to have blockage of the heart arteries.


"We were able to measure blood pressure directly in the arteries of the mice," Crumpacker said. The studies showed increased blood pressure in the infected mice after six weeks, but not in the uninfected group. It also showed that 30 percent of the infected mice in the high-cholesterol group developed atherosclerosis as well as high blood pressure.

Cytomegalovirus is spread through close, personal contract.
Cytomegalovirus (http://en.wikipedia.org/wiki/Cytomegalovirus)


Transmission of HCMV occurs from person to person through bodily fluids. Infection requires close, intimate contact with a person excreting the virus in their saliva, urine, or other bodily fluids. CMV can be sexually transmitted and can also be transmitted via breast milk, transplanted organs, and rarely from blood transfusions.

Although HCMV is not highly contagious, it has been shown to spread in households and among young children in day care centers. Transmission of the virus is often preventable because it is most often transmitted through infected bodily fluids that come in contact with hands and then are absorbed through the nose or mouth of a susceptible person. Therefore, care should be taken when handling children and items like diapers. Simple hand washing with soap and water is effective in removing the virus from the hands.

Just because a disease hits a family particularly hard doesn't mean it's genetic. There are usually better explanations including infectious disease.

Ballet Mom
05-16-2009, 02:08 PM
Hi Dingo,

I just love your research into possibly infectious disease causing at least some of the scoliosis cases out there. I hope to God you are right and that a large portion of these cases and other diseases could just be vaccinated out of existence. Time will tell. Keep up your research. It's fascinating. I'm sending best wishes to you and your son.

Dingo
05-16-2009, 03:24 PM
Ballet Mom

Thanks for your thoughts. My son goes in on Monday at 3:30pm and I'm crossing my fingers that his progression wasn't too bad.

We started strength training, stretching and balance training a week ago. I wish we had started 8 months ago when he was diagnosed but we didn't know what to do.


I hope to God you are right and that a large portion of these cases and other diseases could just be vaccinated out of existence. Time will tell.

I know how crazy it sounds that a back disorder could be caused by an infection but in my opinion it's almost certainly the environmental component behind most cases of progressive AIS. I'll keep watching the headlines. :)

concerned dad
05-16-2009, 09:31 PM
Interesting, Vical Incorporated (VICL) has a vaccine for cmv in clinical trials now.

Dingo
05-16-2009, 10:15 PM
Interesting, Vical Incorporated (VICL) has a vaccine for cmv in clinical trials now.

I'm not sure about the release date on this particular CMV vaccine but I know that scientists have been working on a variety of these (http://topnews.us/content/24468-vaccine-prevent-birth-defects-caused-cytomegalovirus) for a long time. It's my understanding that inside of a decade children and perhaps adults will be vaccinated against CMV.

That's a good thing because CMV is associated with many types of diseases including common birth defects (http://www.marchofdimes.com/professionals/14332_1195.asp), colon cancer (http://www.scienceblog.com/community/older/2002/E/20023308.html) and heart disease (http://www.medscape.com/viewarticle/412227) just to name a few.

Pooka1
06-01-2009, 06:16 PM
Everyone knows that Scoliosis is a common side effect of Polio infection.

Do other infections cause Scoliosis? You bet.

Fish scoliosis triggered by parasite (http://www.cababstractsplus.org/abstracts/Abstract.aspx?AcNo=20053000841)

Horse Scoliosis triggered by parasite (http://www.cababstractsplus.org/abstracts/Abstract.aspx?AcNo=20043001514)

Alpaca scoliosis triggered by parasite (http://www.ncbi.nlm.nih.gov/pubmed/16910858)

Goat scoliosis triggered by parasite (http://www.ncbi.nlm.nih.gov/pubmed/1253609)

Google Search: parasite scoliosis (http://www.google.com/search?hl=en&q=parasite+scoliosis)


Hey Dingo, CD, posted a link to an article with the following statement,

"The pathogenesis of AIS, a condition exclusive to humans, has been the subject of many studies."

http://journals.lww.com/spinejournal/Abstract/2008/12150/The_Pathogenesis_of_Adolescent_Idiopathic.11.aspx

Then the animal models would appear to be irrelevant.

Comments?

Dingo
06-01-2009, 07:00 PM
Pooka1


"The pathogenesis of AIS, a condition exclusive to humans, has been the subject of many studies."

Oops, I guess scientists can make some pretty obvious mistakes. Scoliosis afflicts many animals besides humans. I found those 4 animals with just a few minutes of googling.

Suddenly your quote comes to mind, "Most Published research results are false."

Pooka1
06-01-2009, 07:22 PM
As far as I can tell, they are saying that AIS occurs only in humans and that the causes scoliosises-es-es in other animals are not relevant.

They are not saying scoliosis doesn't occur in other animals besides humans.

Dingo
06-01-2009, 09:51 PM
As far as I can tell, they are saying that AIS occurs only in humans and that the causes scoliosises-es-es in other animals are not relevant.

Adolescent Idiopathic Scoliosis (AIS) is Scoliosis of unknown cause. In the animal studies that I listed the cause is known to be an infection. Whether the two are similar in some way is unknown.

Pooka1
06-02-2009, 06:43 AM
Adolescent Idiopathic Scoliosis (AIS) is Scoliosis of unknown cause. In the animal studies that I listed the cause is known to be an infection. Whether the two are similar in some way is unknown.

Yes but in the identical way that they determined the cause in these other animal models, don't you think they did the same thing with humans and they ruled that out for AIS long, long ago? These guys are very clever as a rule.

I mean if you have a non-human animal model and you had the wherewithal to find the cause of the scoliosis there, why couldn't they do it with humans?

That's why they say AIS only occurs in humans. It means they have ruled out all known causes of scoliosis in any animal and they haven't yet identified the cause in humans. At this point, AIS is unique to humans in the animal kingdom.

Dingo
06-02-2009, 10:21 AM
Pooka1

Idiopathic means of unknown cause. By it's very definition Idiopathic Scolosis isn't confined to humans.

In any case the point is that scientists know that infections cause Scoliosis in animals. They also know that infection with the polio virus can lead to Scoliosis in humans.

PNUTTRO
06-02-2009, 03:58 PM
Yes but in the identical way that they determined the cause in these other animal models, don't you think they did the same thing with humans and they ruled that out for AIS long, long ago?
I mean if you have a non-human animal model and you had the wherewithal to find the cause of the scoliosis there, why couldn't they do it with humans?

Because of ethical concerns, you cannot cause scoliosis in a human. You can only observe it and try to sort out the causes. In animal models, you design an experiment where you change one thing and observe the outcome. Give the animal CMV, mutate a gene, introduce a drug, change diet etc. and then see what happens. Its not at all the same.

My disclaimer to this statement, is that I have no idea if this is what was done in the animals that were cited. I didn't read the details.

Pooka1
06-02-2009, 04:26 PM
Because of ethical concerns, you cannot cause scoliosis in a human. You can only observe it and try to sort out the causes. In animal models, you design an experiment where you change one thing and observe the outcome. Give the animal CMV, mutate a gene, introduce a drug, change diet etc. and then see what happens. Its not at all the same.

My disclaimer to this statement, is that I have no idea if this is what was done in the animals that were cited. I didn't read the details.

I didn't read the papers either. I assumed it was where researchers tracked down the cause of naturally occurring scoliosis in other animal models. If it is where researchers INDUCE scoliosis in animals that wouldn't normally have soliosis then the research is even less relevant than I thought as they are by definition NOT inducing idiopathic scoliosis.

I must admit that possibly didn't even occur to me because then I don't know why Dingo would cite it. It would be completely irrelevant to AIS.

Dingo
06-02-2009, 07:47 PM
Pooka1

Before you hypothesize that scientists purposely infected these animals to cause Scoliosis you might want to read the 4 abstracts.

In any case why would it matter if these animals were purposely infected? The point is that infections triggered scoliosis in a variety of animals.

Pooka1
06-02-2009, 07:54 PM
Pooka1

Before you hypothesize that scientists purposely infected these animals to cause Scoliosis you might want to read the 4 abstracts.

In any case why would it matter if these animals were purposely infected? The point is that infections triggered scoliosis in a variety of animals.

Okay I read the abstracts. They were speculative on the whole.

I don't see the connection to AIS in humans. I don't see any great case is made for a parasitic cause for AIS based on those abstracts. They haven't even shown that the parasite infection was the cause and not some sequelae.

Dingo
06-02-2009, 09:51 PM
Pooka1


Okay I read the abstracts. They were speculative on the whole.

The scientists involved in those studies believed that the cause was infection and I have no reason to doubt their opinions. However in your eyes those cases of scoliosis in animals were idiopathic. Fair enough.

PNUTTRO
06-03-2009, 04:37 PM
The point is that infections triggered scoliosis in a variety of animals.

I read you abstracts: Do any of these descriptions look at all like the human condition?



Horse Scoliosis triggered by parasite

This report documents 6 horses with acquired cervical scoliosis related to a unilateral inflammatory lesion of the dorsal grey column extending over many cervical or cervical and thoracic spinal cord segments


Alpaca scoliosis triggered by parasite

The alpaca's condition continued to deteriorate, and it developed tetraparesis and ataxia and was euthanized after approximately 1 month. Microscopic evaluation of the cervical spinal cord revealed marked vacuolar changes in the left medial portion of the ventral funiculus, mild lymphoplasmacytic infiltration, and multifocal granulomas. The lesions were continuous from C1 to C7 and were compatible with parasite migration.

Goat scoliosis triggered by parasite

An isolated case and an outbreak of parelaphostrongylosis in goats are described. Signs included tetraparesis, hemiparesis, tetraplegia, spastic gait, scoliosis, vestibular strabismus, blindness, and death.

The Fish question is different.
Fish scoliosis triggered by parasite

The authors state:

Myxobolus buri Egusa, 1985, is a well-documented myxosporean parasite that causes the scoliosis of cultured yellowtail Seriola quinqueradiata.

If this statement is true, then it isn't documented in English.

Dingo
06-03-2009, 07:27 PM
Scoliosis triggered by Polio has a lot to do with inflammation in the spine. That might not be too different from some of these. The horse version mentions inflammation.

The AIS we think of is closely related to or caused by a disorder in the nervous system. We don't know why this occurs, it's idiopathic.

If a microbe is triggering Scoliosis in genetically susceptible children it's probably not operating like a wrecking ball the way Polio or those animal cases work. It's probably an autoimmune disease like Narcolepsy or Type 1 diabetes. In case you haven't been paying attention scientists recently proved that Narcolepsy is an autoimmune disease (http://news.bbc.co.uk/2/hi/health/8025662.stm) probably triggered by a microbe.

PNUTTRO
06-04-2009, 10:23 AM
Scoliosis triggered by Polio has a lot to do with inflammation in the spine. That might not be too different from some of these. The horse version mentions inflammation.

The AIS we think of is closely related to or caused by a disorder in the nervous system. We don't know why this occurs, it's idiopathic.

If a microbe is triggering Scoliosis in genetically susceptible children it's probably not operating like a wrecking ball the way Polio or those animal cases work. It's probably an autoimmune disease like Narcolepsy or Type 1 diabetes. In case you haven't been paying attention scientists recently proved that Narcolepsy is an autoimmune disease (http://news.bbc.co.uk/2/hi/health/8025662.stm) probably triggered by a microbe.

All these animals (except the fish-because I couldn't confirm anything) ended up dead.

Just so you know where I am coming from.
I refuse to believe that any of these "animal models" recapitulates the human version of AIS. There are too many different variables. If I wrote a research proposal, citing your examples and said that I wanted to infect fish with a parasite to study the biology of scoliosis because it may lead to a better understanding of human scoliosis, I would NEVER get funding. I would get a criticism so harsh that would probably block me from ever resubmitting the proposal.

Researchers are constantly arguing about how good a animal model really is. We use inbred lines of mice to minimize genetic variability. We try to make genetic changes specific to a particular time in development. We target specific tissues. We attempt to test a single variable at a time and validate results with various tests to make sure that we get a good grasp at the reality.

From my point of view, there a HUGE leaps in logic when you say that a parasite or virus (or whatever your current pathogen is) causing anything that looks like human AIS. I won't believe your argument today or next week or next year.

PNUTTRO
06-04-2009, 10:32 AM
In case you haven't been paying attention scientists recently proved that Narcolepsy is an autoimmune disease (http://news.bbc.co.uk/2/hi/health/8025662.stm) probably triggered by a microbe.

Funny. This article is about a genetic study.

"They pinpointed three specific genetic variants in the same gene in people with European and Asian ancestry that appeared to be associated with an increased susceptibility for narcolepsy."

"Dr Mignot said: "Narcolepsy is probably the result of a series of unfortunate events, starting with genetic predisposition. . ."

"But she added: "Disease expression is rarely the result of one single factor."

Dingo
06-04-2009, 10:50 AM
PNUTTRO


"Dr Mignot said: "Narcolepsy is probably the result of a series of unfortunate events, starting with genetic predisposition. . ."

You cut off the last line

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."

Many diseases (perhaps most) are triggered by a combination of genetic susceptability and environmental damage. If you google Narcolepsy you'll find that the dominant theory is that a virus triggers the immune response, much like Type 1 Diabetes.

LindaRacine
06-07-2009, 03:51 AM
http://www.ncbi.nlm.nih.gov/pubmed/19497680?ordinalpos=1&itool=Email.EmailReport.Pubmed_ReportSelector.Pubm ed_RVDocSum

Three-dimensional spring model: A new hypothesis of pathogenesis of adolescent idiopathic scoliosis.
Yang Z, Xie Y, Li M.

Scoliosis Research Center, Orthopedic Department, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

The pathogenesis of adolescent idiopathic scoliosis (AIS) has been the subject of many studies, but remains little understood. Previous work has shown that there is a correlation between the uncoupled spinal neuro-osseous growth and AIS. We believe that this uncoupled spinal neuro-osseous growth may also contribute to formation of normal curvature of the spine in the sagittal plane during the childhood. We speculate a three-dimensional spring model to better understand our hypothesis. The normal curvature of the spine, the uncoupled spinal neuro-osseous growth, and the overgrowth of the spine in the puberty may be the crucial factors in the pathogenesis of AIS.

Dingo
06-07-2009, 11:18 AM
LindaRacine


Previous work has shown that there is a correlation between the uncoupled spinal neuro-osseous growth and AIS.

That's an interesting link. This work may facilitate a deeper understanding of the mechanical dysfunction that leads to AIS. But there still has to be a cause for this mechanical dysfunction. That's where an infection or a dozen other possibilities might come into play.

PNUTTRO
06-08-2009, 10:02 AM
Many diseases (perhaps most) are triggered by a combination of genetic susceptability and environmental damage. If you google Narcolepsy you'll find that the dominant theory is that a virus triggers the immune response, much like Type 1 Diabetes.

You pose two different models in this thread.
1. an overt infection with lesions and ultimate death of the individual--your animal references.
2. an autoimmune model--narcolepsy, Type I diabetes, and MS.

Which do think it really is?
Or is it something else?

Dingo
06-08-2009, 10:47 AM
PNUTTRO


Which do think it really is?

Infections damage the body in multiple ways. I made my opinion on the cause of scoliosis very clear. Feel free to browse through the thread and read my posts.

PNUTTRO
06-08-2009, 02:24 PM
Infections damage the body in multiple ways. I made my opinion on the cause of scoliosis very clear. Feel free to browse through the thread and read my posts.

But that is the problem. You cite various mechanisms how the parasite/bacteria/virus causes AIS. Toxicity and autoimmune seem to be the most common. I was just wondering if you have a preferred theory.

Dingo
06-08-2009, 04:24 PM
PNUTTRO


I was just wondering if you have a preferred theory.

Children with AIS don't process melatonin properly because of a nervous system dysfunction. I assume that specialized cells in the nervous system have been killed or disabled. This might be caused by autoimmunity like Type 1 Diabetes or Narcolepsy. However it could just as easily be some sort of tropism (http://en.wikipedia.org/wiki/Host_tropism). There are probably a dozen good explanations on how it might work. I don't have a strong opinion on the exact mechanism.

Once scientists determine which cells have been compromised I'm sure they'll have strong opinions on what knocked them out.