Tuesday, September 12, 2006

MZ Twin Discordance

The autism twin study considered the best methodologically speaking found a MZ twin concordance of 60% for autistic disorder and 92% for a broad spectrum. The DZ twin concordances were 0% and 10% respectively. Given that MZ twin concordance is not 100%, people correctly assume that environmental factors must be involved in the etiology of autism. But some go further than that and speculate that the environmental factors must surely be environmental "insults", and that they probably occur post-natally.

This would probably be true if there was no random variation in brain development, and no phenotypical variability due to the social environment. No human phenotype is 100% heritable. Only very simple physical phenotypes, such as eye color, approach that level of concordance.

Let's take White et al. (2002). This study compared the brains of general population MZ twins and found a concordance of over 0.90 for white and grey matter volumes, but only 0.75 for the thalamus, to take one example.

Syndromes known to be genetic in nature can have discordant expression. Kruyer et al. (1994) reports on two sets of MZ twins discordant for Fragile-X. In one pair of sisters, one has mental retardation and the other does not. In each of the pairs the researchers explained the discordance genetically. A Google Scholar search on discordant MZ twins reveals many other such reports.

MZ twins can be discordant for homosexuality. But there is no significant effort to try to pin down the environmental factors involved there. (Hint: It's not likely the vaccines).

Concordance of intelligence is not 100%. It seems to be about 80% for MZ twins reared together, and slightly lower for MZ twins reared apart. Phenotypical variation for intelligence is probably determined by the neurological variability discussed above, plus life experience.

The social environment should not be discounted altogether, as much as people would prefer to. A case in point is that of congenitally blind children, who tend to become autistic.

For those who believe ABA (or some other treatment) works, here's something to ponder. Imagine a pair of autistic MZ twins, one given to a family that believes in ABA and the other given to a family which does not. Can the subsequent discordance be blamed on the one set of parents?

Note that I'm not saying that autistic children are never subject to environmental insult, or that environmental insult does not result in autism-related phenotypical variability. I am simply saying that environmental insult is not necessary to explain MZ twin discordance, as is often argued.

24 comments:

  1. This is excellent. I wish I had read this before writing my critique of Lathe's New Phase Autism. He calls upon as yet unpublished twin studies to support his thesis that environmental insult is causing more autism. This challenges that assumption.

    ReplyDelete
  2. Thanks Mike. What did the unpublished twin studies indicate?

    One problem with twin studies is that their results necessarily depend on how concordance is defined. If it's too narrowly defined, concordance will necessarily be low. An extreme example would be a twin study on intelligence that defines concordane as being within 1 IQ point.

    There's a study by Ritvo et al. which found an MZ concordance of 95.7% and a DZ concordance of 26% as I recall. Clearly, that one must have used a lose definition of autism.

    The extremely high heritability of autism is seen more in the difference between MZ vs. DZ and in the fact that DZ concordance does not appear to be any more likely than sibling concordance.

    If a single environmental insult, such as vaccination, were the key to explaining discordance, then you'd expect pairs of discordant twins to have one insulted twin and one non-insulted twin. (There is one report on a pair of discordant twins which cites perinatal stress in this regard).

    ReplyDelete
  3. IIRC, one frequent problem of separated-twin studies is that it's all too common for one twin to be raised by his/her mother, and another to be raised by his/her aunt, in the same neighborhood. That results in a lot of inadequately-controlled environmental correlation. How well did such studies adjust for the correlation?

    ReplyDelete
  4. Also, the diagnostic criteria for autism are ridiculously subjective. I'm reminded of Lewis Carroll's Humpty Dumpty talking to Alice: "When I use a word, it means what I want it to mean..."

    A pair of twins could have exactly the same behaviors, but if they see different psychologists who don't have the same notion of what a "significant impairment" is, one could get a diagnosis while the other doesn't.

    ReplyDelete
  5. Ebohlman: I don't think there have been any autism twin studies of twins reared apart. They have enough trouble finding 10 or 20 pairs of twins for such studies.

    Abfh: The first autism twin study in 1977 found an MZ concordance of 37% I think, but 89% for "cognitive disorder". The subjectivity there is obviously that they were trying to match for a strict Kanner definition.

    ReplyDelete
  6. Twin studies in Lathe

    First he cites the early studies by folstein and Rutter (1977) and Steffenberg, Gillberg et al (1989) which used more exclusive diagnostic criteria, According to Lathe these studies showed 60 to 100 per cent concordance in MZ twins and zero concordance in DZ twins.

    Then he cites Bailey, le Couteur et al (1995)to show that even with broader diagnostic categories concordance was very high (92%) in MZ twins and very low (10%) in DZ twins.

    The real meat of his argument is in the next three paragraphs which I give in full.

    "Recent data do suggest that the rates of twin concordance are changing. Specifically, the excess of monozygotic versus dizygotic concordance appears to be diminishing. In one study (based on parent/practitioner accounts of zygosity) only 58% of identical twin pairs were concordant versus 36% of non-identical pairs (Croen, L. A., pers.comm.). In an extended twin group, basing concordance and zygosity on parent accounts only, eight identical pairs were concordant, but the majority (21 identical pairs) were discordant; one pair was unclear. A small bias may have been introduced by the selection protocol, but this places identical twin concordance at only 26% (Kates, W., pers comm).
    "In a larger study, including triplets and some quadruplets, applying a strict definition of concordance (V.Kustanovich, Autism Genetic Resource Exchange, pers.comm.), 33 out of 41 (80%)identical twins were concordant but only 17 0ut of 46 (37%) non-identical twins; when wider definition of concordance was applied 41 out of 41 (100%) monozygotic twins were concordant as against 29 out of 46 (63%) non identical twins.
    "Together, these three studies suggest that the nature of ASD is changing, away from concordanc eonly in monozygotic twins, and toward surprisingly high concordance rates (e.g., 63%) in dizygotic twins. This dizygotic concordance suggests evolution away from a purely genetic disorder to one determined centrally by environmental factors, though still with an important genetic susceptibility component."

    The study by Kates, which I mistakenly thought was unpublished is in print: Kates, W.R. et al (2004) in the Am. J. Psychiatry 161, 539-546.

    ReplyDelete
  7. I guess he skipped Ritvo?

    The 0% concordance for DZ twins should not be interpreted literally. It's a consequence of the small sample sizes. It's not possible to say where in the 0-10% range it really is.

    The concordance in siblings seems to be 2-20% depending on how concordance is defined.

    The Kates (2004) study reports MZ concordance for "strictly defined autism" of 0.44. Doesn't give a DZ twin concordance.

    In the Crohen study, yeah, parental reports of zygocity are probably significant methodologically.

    In the Kustanovich study, they must use a very broad definitiion of concordance to find 100% concordance for MZ twins. They could define concordance as "having 5 fingers" and they would find 100% for MZ and DZ.

    There's so much variability introduced by how concordance is defined, that it's impossible to say there's a trend as Lathe concludes. There may be a trend, alright, which is driven by changes in criteria and cultural peceptions.

    ReplyDelete
  8. Hi Joseph,

    This is an interesting post.

    You state that: "I am simply saying that environmental insult is not necessary to explain MZ twin discordance, as is often argued." That may very well be the case, but I’m not sure that the examples that you cite prove it.

    Regarding intelligence, I believe that the nature vs. nurture debate has been settled for most as coming down somewhere in between the two, so it is not surprising that concordance would be 100%, especially as twins age and have different life experiences. Prenatal experience would presumably begin to shape and define the different experiences of MZ twins, and life experiences would only sharpen the differences.

    Regarding White et al (2002), differences in MZ twin brains is not antithetical to the MZ environmental argument, but may in in fact be supportive. The paper appears to describe differences rather than explain causality. The fact that brains differ isn’t the issue (other than to suggest that pure genetics alone is not determinative). The issue is why? Fetal experience (including access to ‘resources’ and environmental stimuli) may provide part of the explanation. If this is the case than it allows for the possibility that the potential for ASD might also be affected (i.e. more than genetics is at play), which also allows for the possibility (which is not the same as proving the case) that such effects could be pre or post-natal.

    Beyond fetal experience, explanations I’ve heard include the potential for brain development to be affected by experience, i.e. the nature vs. nurture debate again. Going back to the comments in my post from a few days ago, I’ll say again that "If autism is experientially caused, as distinct from ASD brain development being impacted by ‘experience’ (suggested in Kates et al to explain cerebellar differences between discordant MZ twins), I would be very interested in finding out more." But for what it’s worth, I didn’t see in the White et al (2002) abstract a case being made that the differences between MZ twins were non-environmental, but in fact potentially the opposite - "The surface measures, however, demonstrated the least correlation within twin pairs and thus are more prone to environmental influences." (emphasis added)

    I’m not sure how homosexuality plays out in the brain, or what the research suggests on this, other than I seem to recall reading something suggesting that there are brain differences in at least some cases. Again, the issue is not just whether differences exist (and I don’t know if they exist between MZ twins discordant for homosexuality), but why they exist. "Why" answers the genetic vs. environment question. Merely describing that a difference exists does not.

    The Kruyer et al (1994) study is interesting in that it shows that the transition from premutation to full mutation can occur postzygotically, suggesting in the MZ brothers that due to the CGG repeats that they were not in fact genetically identical. The issue with the twin girls was due to methylation status, which would fall under the label of epigenetic. A couple of thoughts on this. First, given that fragile X is a mutation, and apparently not a very stable one, given the variation in the degree of mutation within those affected, it is not totally surprising that the mutation remains unstable during early fetal development. In the second case, methylation status is the ‘second hit’. So, is autism a mutation? Possibly in some cases. In all? I would suggest that this is doubtful, and that these two cases cannot prove or disprove an effect beyond genetics in a majority of ASD cases (in the latter they actually support it – next question, why did the methylation status differ? Environmental effect?).

    Regarding the effects of the social environment, to me it is obvious that this could have a significant effect on outcome for any child, ASD or not, but I’m not sure that it could ‘cause’ autism in the same way it can ‘cause’ differences in intelligence or potentially even sexual preference. If one can ‘cause’ autism via socialization then this moves us in a very interesting - and to some (many?) a potentially very objectionable - direction.

    Regarding “For those who believe ABA (or some other treatment) works, here's something to ponder. Imagine a pair of autistic MZ twins, one given to a family that believes in ABA and the other given to a family which does not. Can the subsequent discordance be blamed on the one set of parents?”

    Er, wouldn’t the discordance be ‘blamed’ at least in part on the effects of the treatment? Isn’t the expectation of ‘change’ (whether realized or not) the reason why people follow various intervention strategies?

    Overall, I’d suggest that your examples lend support to the case for a more widespread environmental impact (epigenetic or other) in all people, rather than suggest that it is not necessary to explain MZ twin discordance for ASD. Not all non-genetic effects have to be deleterious. Unfortunately, some of the terminology is rather pejorative, e.g. ‘insult’ or ‘second hit’, but there is nothing to say that an added stimulus (or stimuli) that might affect ASD needs be other than innocuous to most people. Two examples (not referring to ASD) are peanuts and bee stings. To most people the former is quite edible and the latter is a painful annoyance to be avoided, but to some the effects of one or the other of these can be catastrophic. There is nothing to suggest that any ‘insult’ or ‘second hit’ that may result in ASD needs to be universal in effect or that susceptibility would be universal. In addition, in a comment on my blog you suggested that “ The 'second hit' idea sounds like a vaccination event or something. I think environmental influence works in more subtle and random ways.” But as I replied, ”‘Second hit’ is a term I have seen in the literature referring to causes above and beyond the obvious genetic links, and where I’ve seen it the words were not used to specifically indicate or suggest a discrete event.”

    You closed stating ”I am simply saying that environmental insult is not necessary to explain MZ twin discordance, as is often argued.” If you narrowly define environmental insult as a vaccination, then I’m inclined to agree. But if you have a wider definition of the term then I would suggest that the case has not been proved, other than based on continuing mutation in a potentially small number of cases. This brings to mind in my childhood the example of seeing a three wheeled car in England. It illustrated that three wheeled cars are a realistic possibility. But I would still suggest that the probability that the next car I see has four wheels is extremely high. In the case of ASD, an isolated example of how discordance can be genetic only is not the same as proving that most examples of discordance have no environmental cause.

    Regarding Mike Stanton’s citing of Lathe, I would suggest that the Autism Genetic Resource Exchange is a voluntary mechanism, and that participation could not be assumed to be representative of the general population. If so, this would suggest that Lathe could not fairly draw the conclusion that MZ vs. DZ prevalence is changing (or that it is not) based on extrapolating prevalence over time from AGRE data.

    ReplyDelete
  9. This is what I see.

    There are some very fanatical parents, and some not so fanatical parents, who do not want to think that their genes could be anything less than ideal.

    They are told, "You have an autistic child."

    They respond, "Why?"

    The doctors say, "We don't know why, but autism is the MOST highly heritable mental/developmental disorder of all, so it's likely that your genes had a lot to do with it."

    The parents: "Huh? I'm not autistic. No one in my family is autistic! This does not make sense. Are all cases of autism genetic?"

    The docs: "No, some cases can arise from prenatal infection, like with rubella... and some cases can come from prenatal drug exposure..."

    Parents: "But we were immunized against rubella as were all the children within a 5 state area, we weren't exposed to rubella. And my wife never took thalidomide, or valproic acid, or anything but a little aspirin, she doesn't drink alcohol or take street drugs... our babies were conceived naturally, not with exotic technologies. Why is our baby autistic?

    Doctor: "It could be your genes."

    Parents: "But we told you there aren't any autistic people in our family."

    Doctor: "It could still be your genes."

    Parents: "But our genes are GOOD! We don't make damaged babies like this. Our people are fine stock..."

    Doctor: "It could still be your genes."

    Parents: "What's this about identical twins and autism?"

    Doctor: "If one of a set of MZ twins is autistic, it's very likely that they both will be on the spectrum, even if they both aren't 'classic" autistics."

    Parents: "So it's not all genetics? See! I told you it's not all genetics! (huffy) I knew we had good genes. We are superior people, we have GOOD genes. I don't have twins, but I know that I had a normal baby and that I've heard it's the vaccines. Must be the vaccines."

    Doctor: "It could be just your genes and random uncontrollable experiences that make the difference between the MZ twins."

    Parents: "It's not just genes. It's the vaccines. That's obvious. You doctors are trying to cover up the conspiracy to protect vaccines, which are evil and the source of all disease and death.... I read it last night on the Internet on Yahoo! groups... We're out of here."

    ReplyDelete
  10. Hi

    Camille you said

    "There are some very fanatical parents, and some not so fanatical parents, who do not want to think that their genes could be anything less than ideal"

    I am not fanatical - even a bit- and I have not problem about having /being into the BAP myself and I have accepted that genetics has a lot to do with the fact that my son is autistic.

    What I can not understand is the oversimplification - once and again not only of the situation, but also of my feelings or my thoughts about-.

    No, I am not represented by any of your words about.

    Having a strong experience with my son, I consider that my own path and elections on him have a lot to relate with science/clinical facts and nothing to relate with beliefs.

    Joseph
    Again, I am going to cite genetic epidemiology. From a website related to- that I included in Ian´s blog- I will include some key points to consider in the case of MZ vs DZ studies.

    "The usual assumptions of a classic twin study are random mating, no interactions between genes and environment, and equivalent environments for MZ and DZ twins. In the study of a complex trait, phenotypic variance is divided into a component due to inherited genetic factors (heritability), a component due to environmental factors common to both members of the pair of twins (the shared environmental component), and a component due to environmental factors unique to each twin (the nonshared environmental component). Twin studies have been used to establish the presence of a genetic component in the etiology in many diseases (MacGregor, 2000) including celiac disease (Greco, 2002), Alzheimer's disease (Raiha, 1996), schizophrenia (Sullivan, 2003) "

    Alternatively, twins discordant for disease have been used to examine possible environmental causes. Adoption studies also permit the separation of childhood rearing effects from genetic effects by studying the similarity of adopted children with their biological and foster parents. The assumptions are that the resemblance between an adopted child and biological parent is due only to genetic effects, while that between the adopted child and the adoptive parent is only environmental in origin (see ... the Colorado Adoption Project website for adoptee studies). However, sometimes the representativeness of adoption studies can be questioned due to special circumstances surrounding adoption (adoption bias). In contrast, twins are born into all classes of society (Hublin & Kaprio, 2003). Migration studies also provide clues for genetic vs environmental causes (Parkin & Khjlat, 1996; see also Ecological Studies). If the incidence in migrants revert to the host population's incidence, this suggests stronger environmental factors in pathogenesis (as in diabetes (Drash, 1990) or hypertension (He, 1991).
    An example of an study on diabetes
    Schweiz Med Wochenschr. 1990 Jan 20;120(3):39-45. Related Articles, Links


    What do epidemiologic observations tell us about the etiology of insulin dependent diabetes mellitus?

    Drash AL.

    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children's Hospital of Pittsburgh, Pennsylvania.

    Noninsulin dependent diabetes mellitus (NIDDM) is associated with an entirely different set of genetic alterations from insulin-dependent diabetes mellitus (IDDM). Over 90% of IDDM carry HLA type DR3, DR4 or both. Several theories have been proposed to explain how the genetic alterations are translated into a beta cell destructive process. All involve the elaboration of a beta cell autoantigen. A major current research focus is on the development of pharmacologic approaches to the control of the beta cell destructive process (cyclosporine A). This has led to a shift in interest to the early identification of individuals at risk for IDDM. Many questions remain to be answered. In our paper emphasis is placed on epidemiological research. In Allegheny County, Pennsylvania, we have found an incidence of 1.73 cases/1000 (incidence rate of 15/100,000/year). There were marked geographical variations (incidence rate of 1/100,000/year in Asian countries, of 40/100,000/year in Finland). This suggests that there are major environmental determinants leading to expression of disease in genetically susceptible individuals. There are no geographical differences in the main age of onset, the sex ratio and the clinical patterns in the initial course of newly detected IDDM. In all parts of the world islet cell antibodies are positive in 60-80% of newly diagnosed IDDM. Migration of children from their native homeland with a low incidence rate to a country with high incidence rate was accompanied by an increase of incidence. The following potential environmental factors have been considered: viral infections, environmental toxins, nutrients, and stress. In our view IDDM occurs in genetically susceptible individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

    With the amount of confounding variables on ADS epidemiology- a similar approach can not be discarded, in advance, because, at difference with diabetes, we have no clinical biomarkers of ASD- yet.

    MAría Luján

    ReplyDelete
  11. Camille: LOL.

    Ian: Are you saying that if White et al. had done their study on prehistoric humans, they might have found close to 100% concordance for brain areas? I would tend to doubt that, but it would be of interest if it were true. I think random variation is inevitable.

    With a study like White et al. it would be interesting to know if the discordance is prenatal or postnatal, early or late.

    The ABA example is not that good. I'd change that with RDI, which is untested but many people swear by it. It's said not to be a therapy, but a "lifestyle". That "lifestyle" could presumably come naturally to some families.

    Parent-blame is misguided and unproductive, and still common place with many other psychiatric conditions. The social environment, however, should not be considered irrelevant on that basis. From studies of twins reared apart, I understand the environment outside the family trumps the family environment anyway.

    The nature vs. nurture debate is often simplistic. There isn't a single answer - it depends on the environment really.

    ReplyDelete
  12. María: There are well known limitations of twin studies, and some argue twin studies are pseudoscientific. I think it's important to understand what the limitations are before deciding if they have any merit. One important limitation is that zygocity is usually not determined genetically, but based on physical markers. Another problem is that twins may be special in the population studied (e.g. there used to be speculation that twins are at higher risk for autism). Yet another problem is that the social environment of non-indentical twins may not be shared as much as that of identical twins.

    Even with these considerations, I think there's a lot to be said for autism twin studies.

    I'm not sure what your point is regarding the diabetes study. But I would note that concordance for a medically measurable disease such as diabetes or cancer is not the same as concordance for something that is measured by observing behavior. To make that a better analogy, we would need to look at concordance for the subjective symptoms of diabetes.

    That's why I think something like personality makes for a better comparison. And you'll find that personality turns out to not be very heritable.

    ReplyDelete
  13. Hi Joseph

    It was not my intention to compare autism with diabetes/ other strongly genetically-based medical conditions. My point was the approach, from the epidemiological point of view.

    And this is exactly my point
    But I would note that concordance for a medically measurable disease such as diabetes or cancer is not the same as concordance for something that is measured by
    observing behavior.

    It is not, but because of the absence of knowledge about what are the true effects of ASD genetics in biochemistry (through epigenetics) in terms of having a set of biomarkers to correlate. As you know, there are recent manuscripts - and not so- about serotonine levels or BNDF levels for example in ASD to mention a few- and I am not talking of only one biomarker.
    Again, and even when confounders can be present, I also do think that twin studies are important in ASD. What I do think is that the environmental non-shared contribution and the shared contribution can not only be considered emotional/pshycological/parental/social in advance, but also must be related to the nutritional status/biochemistry/toxicology/immunology to have a complete picture. And in this sense the genetic epidemiology has a lot of tools to evaluate the component. And ASD has not been studied with it.
    MAría Luján

    ReplyDelete
  14. Joseph wrote:

    "Ian: Are you saying that if White et al. had done their study on prehistoric humans, they might have found close to 100% concordance for brain areas?"

    No. My use of the term environmental goes beyond industrial or post-industrial pollutants to cover pretty much any exogenous factor that could interact with the organism. These have always existed (e.g. 100,000 years ago the availability of a good supply of animal protein would be an exogenous factor), although the last couple of centuries have definitely added some new factors into the mix.

    My next post (soon?) will better explain what I'm getting at, but it is a bit too long an argument to state partially formed in a comment. I would ask though, why does everyone seem to think 'environment' automatically has to mean vaccines? As Maria Lujan points out, other areas of examination could include nutritional status, biochemistry, toxicology, and immunology. Whatever happened to diversity of thought?

    ReplyDelete
  15. why does everyone seem to think 'environment' automatically has to mean vaccines?

    I'd ask that in EOHarm. Maybe we should ask Brad or John.

    ReplyDelete
  16. "I'd ask that in EOHarm. Maybe we should ask Brad or John."

    Okay, now how does that relate to my comments? You, Kristina Chew, Brett (29 Marbles), and ABFH are all part of the Autism Hub. Should I assume that there is no daylight between the four of you?

    ReplyDelete
  17. Joseph
    By one extremist side of the debate, there has been an overemphasis on thimerosal/vaccines as CAUSES of autism- even when I think as always that they must be studied and considered with care because of individual susceptibility.
    But for "this" side of the debate, in the attempt to dismiss the CAUSALITY per se of vaccines/thimerosal another extremism has been developed: vaccines has nothing to do- NEVER has and NEVER will.
    And nobody has conclussive proofs of nothing, at this point BUT a high amount of published clues about negative reactions to vaccines can be found and an extremely high amount of anecdotical evidence that nobody seems to be interested on- BTW, I live one anecdotal evidence. Biological plausibility is present, but as a part of a very much wider environmental component, when ALL the sources are important to consider , IMHO, and where ALSO the immunological stressors have been historically dismissed in ASD.
    And it seems that every time that I post here ( or in other blogs) implicitly the defense is " but vaccines are not" , "but it is unlikely vaccines" even when my proposal is much more wide and global in terms of strong candidates and is related to a true debate, that unfortunately is virtually impossible because of the situation.For me HM and vaccines yes have their place but with an objective look at the issue that today everywhere- but very selected places in the blogosphere-is lacking.
    Even more, I consider that all of us are different. In the Autism- hub there are many different ideas and styles present. In the biomedical field there are as many ideas/styles/conclussions as parents.
    Why is so difficult to find a different view-more objective- than the answer in advance of a question/prompt that is considered implicit- that is not ? Now, if you consider that you found the truth, therefore this is not a place to debate, but a place of reaffirmation of an adopted position on the issue . Honestly, it would be important for me to know, because I do not want to disturb anyone with ideas that are considered without interest for you and this is your blog.
    Thank you
    MAría Luján

    ReplyDelete
  18. Okay, now how does that relate to my comments?

    It does not. It was in answer to the question "why does everyone seem to think 'environment' automatically has to mean vaccines?"

    That's used as an example. Could it be because 90% of the focus in the autism community regarding environmental factors is vaccines? It's only lately that people have begun to look at environmental pollution, for example. There are really no significant efforts to look at other things you mentioned, such as the ideal nutrition of an autistic person, which might actually be of some use.

    ReplyDelete
  19. María: The case against thimerosal is conclussive. It's like beating a dead horse at this point. It's fine to keep an open mind, but there are limits to that. Not only has the prevalence of autism not dropped in any age cohort as thimerosal is phased out, do you know of any effect on any health outcome that phasing out of thimerosal has achieved? It's hard to accept the individual suceptibility argument if there's no observable effect.

    There's also considerable evidence against the idea that MMR is related to autism.

    For the rest of the ingredients, isn't it reasonable to suppose it's just more of the same?

    ReplyDelete
  20. Joseph

    My analysis is totally different.
    Epidemiology, such as it has been done, can not answer biologically and genetically/epigenetically based questions.

    The case against thimerosal is conclussive.
    Your opinion

    It's like beating a dead horse at this point.

    Your opinion
    It's fine to keep an open mind, but there are limits to that.

    Open mind must not have limits.

    Not only has the prevalence of autism not dropped in any age cohort as thimerosal is phased out, do you know of any effect on any health outcome that phasing out of thimerosal has achieved?

    The analysis is not so simple

    It's hard to accept the individual suceptibility argument if there's no observable effect.

    There is, but it has not been
    properly studied yet. There is only non-systematized anecdotic evidence.

    There's also considerable evidence against the idea that MMR is related to autism.

    Your opinion

    Sorry, I disagree with everything
    MAría Luján

    ReplyDelete
  21. Maybe the concept of monozygotic or even twin is just a construct of dubios validity in the cosmos of dark matter (conveniently invisible what) and silent trees.

    Humpty Dumpty I say, I am even quoting Ludovicus Carolus in my linguistic onslaught on the social model of disability where one word is swapped for another.

    Tis a system and you can only argue within it, without it and outwith it withall it falls and all the kings horses etc ..... :)

    ReplyDelete
  22. Concise and excellent Joseph, as usual.

    ReplyDelete
  23. Larry: I suppose that's the fluent Larryese you were talking about? :)

    Jonathan: Thanks.

    ReplyDelete
  24. Southeast and main Asian pandora jewelry countries have twisted rubies for centuries, cheap pandora bracelets but research as to where, and how to find more deposits is Pandora charms spare, and production has figured out how and mining companies,” Pandora beads Giuliani says, to look at exactly the right time and place.” pandora set Farther investigation of claret formation, based on tectonic scenery, cheap pandora geochemistry, fluid inclusions and isotopic ratios, allowed discount pandora Giuliani’s lineup to remodel a new prototype for the French Institute pandora 2010 of Research for Development (IRD) and the National Scientific pandora sale Center of Research, two government-sponsored knowledge Pandora Bangles and technology research institutes that aim to aid in the sustainable cheap pandora bracelets development of developing countries. Before the collision pandora bracelets prices of the Eurasian and Indian plates, lagoons or deltas sat in the regions where marble is giant, pandora bracelets and charms he says, “and there is the brains to expect that the new pandora bracelets sale thoughts should help development of the artless capital.” discount pandora bracelets Virginie Garnier, Gaston Giuliani and Daniel Pandora necklace Ohnenstetter urban the shape to do just that. They work for the garnet cheap pandora charms genesis. While studying the bedrock in Vietnam in 1998, the discount pandora charms French players found rubies, which detained traces of aluminum, chromium pandora charms sale and vanadium from universities, international corporations, governments pandora charms 2010 and why the rubies got there, and has created a paradigm Pandora beads to help these evaporites, Garnier says, when the Eurasian cheap pandora beads and Indian plates collided, raising the Himalaya Mountains.

    ReplyDelete