Talk:Heritability of autism

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[edit] General (multicausal) theories

I moved the following subsection, recently contributed to Causes of autism by User:Idealiot in this edit, to this talk page, as Causes of autism merely summarizes genetic causes and references Heritability of autism as the main page for the subject. I'm leaving this section here for genetics editors to see and use if they like. The only scholarly reference I've found to the 1993 publication in question is a 2000 paper by the same author. Eubulides 04:39, 26 July 2007 (UTC)

Thanks Eub for keeping my words in sight, but really it does belong not here but on the autism causes pages (as I explained on that talk page). I propose to abridge the piece and move it back to the causes page (draft abridgment follows immediately below). E wrote "The only scholarly reference I've found to the 1993 publication.." - but so what? More to the point not a single fault of reasoning or evidence has been shown. Loads of the greatest discoveries were totally ignored/derided for decades by "distinguished experts", so that comment is merely an exhibition of ignorance. And many people would consider Rimland's ARRI to be ultra-high in the scholarship rankings anyway -he did only revolutionise the field twice (debunking refrigerator mothers; first recognition of increase data).--Idealiot 14:05, 26 July 2007 (UTC)

[edit] General reduction of gene-expression

This is a “general” theory of autism causation not least in that it integrates together a diversity of environmental and genetic factors into a unified autism/high-IQ factor of general suppression of gene-expression.

The paper relates that concept to a seemingly comprehensive review of autism data including social class and gender differentials and otherwise-puzzling observations such as the hand-flapping and posturing. It declares that no-one has found any incompatible evidence or error of reasoning. It claims that autism involves primary abnormalities in diverse parts of the brain.

The theory was favourably mentioned by Bernard Rimland in his Autism Research Review International in 1993 and 1994. No published criticism is in evidence (highly unusual for a theory of any substance).

A pdf reprint is available free at http://cogprints.org/5207

Pre-abridgement version:

[edit] General reduction of gene-expression

This gene-expression theory of autism was published in 1993 (pdf reprint free at http://cogprints.org/5207).

It is a “general” theory of autism causes in that it integrates together a diversity of environmental and genetic factors into a unified autism/high-IQ factor of general suppression of gene-expression. It thus appears to be compatible with several of the other (more specific) causal hypotheses, and indeed supportive of them. It claims to refute the commonly-stated notion that autism remains a puzzling mystery yet to be solved.

The paper relates its “antiinnatia” concept to a long putatively comprehensive list of autism characteristics compiled by L Wing and others. It declares that the author has been unable to find any incompatible evidence. Data on the social class and gender differentials are also given explanation, as are otherwise-puzzling observations such as the hand-flapping and posturing.

The theory suggests that autism involves primary abnormalities in diverse parts of the brain and in diverse psychological functions. Random binding to DNA is proposed as one concrete mechanism of the antiinnatia.

The theory was favourably mentioned by Bernard Rimland in his Autism Research Review International in 1993 and 1994, but otherwise it appears to have been ignored. No published criticism is in evidence (an unusual situation for a theory of any substance).

The reprint’s webpage states that a paper giving update information relating to this paper, confirming three predictions and providing resolution of the later autism increase controversy is in preparation. As of 24th July 2007 there is no sign of this update.

[edit] Comments on Clarke's theory

As I explained in Talk:Causes_of_autism#General (multicausal) theories this is a gene-expression theory that most people would file under genetics, —This is part of a comment by Eubulides , which got interrupted by the following: <<No, it is a causes of autism theory which they would file under causes and not genetics. Just your peculiar idea there. Any halfbaked excuse to remove from the causes page basically.>> so it belongs in this (genetics) page not the more-general causes page. As for the quality of the theory itself, I'm not convinced it deserves so much coverage here. —This is part of a comment by Eubulides , which got interrupted by the following: <<Sorry, why should anyone give a d about your personal opinion of its merits? How about that of Rimland who was ever so slightly more distinguished in the field? How many of those other theories did he mention in his ARRI? What solid reasons for holding a low rating of it??? (If you consider ignoring by others to be a sound reason for ignoring then you put yourself in the same fool-bin as those who dismissed numerous great works such as stat thermodynamics, circulation of blood, plate tectonics, etc etc etc ad nauseam . Go on just do it.)>>

One brief sentence would be plenty. —This is part of a comment by Eubulides , which got interrupted by the following: <<How about applying that concept to your own excessive halfbakery here?>>

The test of a theory is not merely whether it has ever been refuted, but whether it is useful. —This is part of a comment by Eubulides , which got interrupted by the following: <<Who says so, and on what basis?>> This one has not been useful. —This is part of a comment by Eubulides , which got interrupted by the following: <>Evidence please. I have already mentioned that numerous of the greatest (Very useful) discoveries were ignored for decades by narrowminded "superior" contemporaries. Why should the usefulness opinion of mere you count for so much? I have to say that your own efforts here have distinctly negative usefulness, indeed approximating to functioning as a troll.>>

I've found one mention of it in a peer-reviewed publication (by the same author). —This is part of a comment by Eubulides , which got interrupted by the following: <<which is a point I have already shown to be ridiculous in the heritability talk page (see preceding para here).>>

The author himself has apparently moved on to saying that the theory is confirmed by the fact that autism is associated with watching television, and that mercury amalgams are the cause of recent autism increases; see Clarke's 2006 tribute to Rimland, so the theory is not languishing for his lack of trying. Eubulides 16:35, 26 July 2007 (UTC)

Not at all. The theory is distinguished by a huge lack of promotion by its author, partly for reasons he briefly indicates in that tribute. Persistent obstruction by negative busybodies does not help either (exactly as encountered by numerous greatest discoveries in the past). Eub evidently adheres to a fallacious notion that establishment dogma = consensus = ok to present as absolute truth on the wiki pages. "Useful" for making oneself popular but not much else. --Idealiot 00:16, 27 July 2007 (UTC)
Please see WP:UNDUE, particularly the segment "If a viewpoint is held by an extremely small (or vastly limited) minority, it does not belong in Wikipedia (except perhaps in some ancillary article) regardless of whether it is true or not; and regardless of whether you can prove it or not", and WP:COI, WP:REDFLAG (particularly the line "Claims not supported or claims that are contradicted by the prevailing view in the relevant academic community. Be particularly careful when proponents say there is a conspiracy to silence them.") and WP:FRINGE. If it's not supported by the mainstream, you will have to be patient until it is, not champion it here. Wikipedia is not a soapbox. WLU 12:55, 27 July 2007 (UTC)
I concur with WLU. SandyGeorgia (Talk) 16:06, 28 July 2007 (UTC)

[edit] talk header added

I've added the talk header because this page is hard to read; signing talk page entries would be helpful. SandyGeorgia (Talk) 15:59, 28 July 2007 (UTC)

[edit] glutathione S-transferase polymorphs and ASD

I Just stumbled upon the following in this article about environmental factors and mental health in this latest issue of Environmental Health Perspectives:

Research in the April 2007 issue of the Archives of Pediatric and Adolescent Medicine showed a positive correlation between a diagnosis of autism in children and a polymorphism in a gene coding for the enzyme glutathione S-transferase in their mothers. These enzymes are involved in the detoxification of endogenous compounds such as peroxidized lipids, and in the metabolism of xenobiotic agents. The researchers determined the frequency of glutathione polymorphisms in 137 members of 49 families with a history of autistic spectrum disorders. Mothers of children with autism were 2.7 times more likely to carry the GSTP1*A haplotype. The results suggest that the haplotype “may be acting in mothers during pregnancy to contribute to the phenotype of autism in the fetus.” Source: Williams TA, Mars AE, Buyske SG, Stenroos ES,Wang R, Factura-Santiago MF, et al. 2007. Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype. Arch Pediatr Adolesc Med 161(4):356–361.

Anyways, I don't see any mention of this gene in this article, so I thought I'd bring it up here. Yilloslime 18:30, 3 August 2007 (UTC)

Thanks for the heads-up. I added a brief mention. This part of the article needs a good rewrite to turn it into a decent review, but that's a bigger task. Eubulides 22:47, 3 August 2007 (UTC)

[edit] Neurexin 1

http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=NRXN1&first=+Find+&start=5378 references NRXN1 as part of chromosome 2 and not 11, but I'm not a specialist, please confirm Agravier (talk) 22:23, 23 December 2007 (UTC)

Right you are. Thanks. I fixed it. Eubulides (talk) 21:05, 5 January 2008 (UTC)

[edit] Categorization of autism-related genes

Today's Science has an editorial that has a nice categorization of autism-related genes. Perhaps we could use that instead of our home-grown one? Here's a citation (it's not in Pubmed yet so I'm leaving that blank for now):

Eubulides (talk) 17:17, 11 July 2008 (UTC)

[edit] Qualification added to lead

This change added the qualifying language "Based on available but limited scientific knowledge" and "thought to be" to the lead. The cited sources do not use qualifying language like that; for example, Abrahams & Geschwind 2008 (PMID 18414403) say "Autism has a strong genetic basis. Several lines of evidence support genetic factors as a predominant cause of the ASDs." I know of no reliable sources disagreeing with this claim. I tried to improve the situation by rewriting the lead sentence, citing Abrahams & Geschwind. Eubulides (talk) 14:37, 7 August 2008 (UTC)

The new lead is better. But read the the source you cite carefully. "A strong genetic basis" and "several lines of evidence support" is not as conclusive as the original wording you proposed, or even very conclusive at all. It basically means how I originally rewrote it - research in the field has failed to make many definitive conclusions, and much uncertainty is still associated with the etiology. There is much stronger evidence, for example, that alcoholism has a strong genetic basis, but nobody in their right mind would say that genetics cause alcoholism. The article itself points out how uncertain it all is. --Leifern (talk) 17:29, 7 August 2008 (UTC)
The original wording is supported by other reliable sources; whether we use it, or the current wording, is as much a style issue as anything else. There is certainly room for further research in the field, but the mainstream consensus is that autism is "overwhelmingly genetic" (see, for example, Garber 2007, PMID 17626859). For autism a typical heritability estimate is around 90%, for alcholism it's around 50 or 60%, so the mainstream consensus is that autism is much more strongly influenced by genetics than alcoholism is. The uncertainty in autism is over which genes are involved, not over whether genes are involved at all. Eubulides (talk) 19:14, 7 August 2008 (UTC)
Much more research has been done on alcoholism, and therefore the 50% - 60% number has a higher degree of confidence. The overwhelming consensus is that they have absolutely no idea why some kids and not others are afflicted with autism, but have concluded there is a strong genetic component. Duh. Not very helpful, when they also have no idea what genetics are involved. As the article points out. It would be misleading to the extreme to imply or express that the books are shut on autism. It's still being diagnosed as a psychiatric disorder, based on vague behaviors. There is no blood test, no genetic markers, nothing that provides anything approaching a definitive diagnosis. So, no, it's not a style issue. It's a matter of being scientifically precise; and not overstating the state of science on this matter, which is very very primitive. To put it kindly. --Leifern (talk) 20:06, 7 August 2008 (UTC)
Your arguments are largely original research (and the "absolutely no idea" is a stretch relative to what is known about genetic factors), while Eubulides edits are reliably sourced and in accordance with WP:UNDUE. SandyGeorgia (Talk) 20:13, 7 August 2008 (UTC)
Original research? I am pointing out that scientific knowledge is limited in this field. How is this original research? If you're going to throw out accusations like that, kindly substantiate them. --Leifern (talk) 11:50, 8 August 2008 (UTC)
It's not true that "much more research" has been done on the heritability of alcoholism. The two bodies of research are roughly comparable these days. It's also not true that researchers "have no idea what genetics are involved". In some cases they very well do know (see, for example, Stephan 2008, PMID 18179879) and there are indications that the percentage of such cases is growing (see, for example, Beaudet 2007, PMID 17479094). Leifern's summary of autism genetics seems to be based at least partly on the state of the art 10 years ago, but a lot has happened since then; see, for example, O'Roak & State 2008 (doi:10.1002/aur.3). Eubulides (talk) 07:57, 8 August 2008 (UTC)
OK, I'll concede I'm not up on the research on alcoholism. My only point is that to implicitly and explicitly attribute autistic spectrum disorders solely to genetic factors is misleading, because a) the research itself only points out that there is a strong genetic basis for some portion of these disorders, which is qualitatively not a lot more meaningful than saying that alcoholism has a strong genetic component; and b) it overstates - vastly - the amount that is actually known about the disorders. I am happy to be proven wrong: refer me to a genetic test that provides a strong diagnostic foundation for autism spectrum disorders, in the way you could for, say Turner syndrome, Prader-Willi syndrome/Angelman syndrome, or even a predisposition as with Parkinson's disease; both I and the scientific community would be happy to know about it. --Leifern (talk) 11:50, 8 August 2008 (UTC)
Neither the old nor the new text attributes autism or ASD "solely" to genetic factors. The 90% heritability estimate for autism is qualitatively different from the 50% to 60% estimate for alcoholism: autism is the most heritable of any major psychiatric condition. Saying that autism is "overwhelmingly genetic" is not at all the same thing as saying we know the exact genetic mechanism: it is possible (via twin studies) to show that a condition is overwhelmingly genetic without knowing which genes are responsible. As for genetic tests, again, please see Stephan 2008 (PMID 18179879); this does not discuss a simple Mendelian test for all of autism (we will never find a test like that), but it does discuss CNTNAP2 mutations that cause one subtype of autism. Autism genetics has made great strides in the last few years; it's hard even for the experts to keep up. Eubulides (talk) 17:09, 8 August 2008 (UTC)
For starters, autism is not a psychiatric condition. I think everyone but the ghost of Bruno Bettelheim agrees that is'a a neurodevelopmental problem, and is probably a broad description for several underlying disorders. There are also credible points of view that it's not one condition, but it seems that there is a lot of trouble figuring out how to separate them. Also, in this day and age genetic testing is not limited to Mendelian tests, and nobody is arguing that it should be. In fact, the examples I mention require increasingly sophisticated genetic tests to be precise, and research shows there is quite a bit of nuance. The issue I have is with the premise that science can explain the level to which "autism" can be explained by genetics. The research you cite indicates a very primitive state of the art, and as an editorial aside, it appears that Occam's Razor has gone out the window. What is clear is that genetic plays an important role, but it is not clear how big of a role it plays. I just don't want us to overstate a point there is no basis for. --Leifern (talk) 20:58, 8 August 2008 (UTC)
  • Autism is defined by recent reliable sources as a psychiatric condition. See, for example, Sutcliffe 2008 (PMID 18452756), which says of autism "How then to index the dimensionality of a complex, behaviorally defined psychiatric condition?"
  • Quite possibly you are correct that autism is a broad description for several underlying conditions. But that is not inconsistent with autism's observed heritability of around 90%.
  • Again, twin studies can be used to show that genetics plays an important role, even if we don't know which genes are responsible.
  • Many reliable sources agree on the overwhelming contribution of genetics to autism. If we limit ourselves only to refereed medical journal review articles published so far this year, these sources include Abrahams & Geschwind 2008 (PMID 18414403), Fisch 2008 (PMID 18666231), and O'Roak & State 2008 (doi:10.1002/aur.3). I don't know of any sources of this quality that disagree.
Eubulides (talk) 00:58, 9 August 2008 (UTC)

[edit] Phenocopies

Does the section on phenocopies have support in the literature on autism? The definition of that word:

an environmentally induced phenotype mimicking one usually produced by a specific genotype.

implies really that we know the genotype (or a small set of genotypes) that cause autism. Also, fragile-X syndrome, Rett syndrome and tuberous sclerosis (TSC) are not environmentally induced diseases. The autism article makes it clear that it is diagnosed on behaviour, not cause or mechanism (though Rett syndrome is specifically excluded). That allows for someone with TSC to be diagnosed with autism, rather than it merely being described as "autism-like", which is the term this article uses.

The autism article divides it into syndromal and non-syndromal autism, with the former including TSC. This paper uses "idiopathic" (primary) and "secondary" to distinguish groups, with the latter including "a known environmental agent, chromosome abnormality, or single-gene disorder". The paper gives figures (5-10%) for the secondary-autism group, which is a figure this article doesn't contain. Colin°Talk 12:16, 2 September 2008 (UTC)

To be honest I had never read that section. I agree that it's not supported by the literature, and removed it. For what it's worth, that "5–10%" is growing with time, e.g., Steyaert & De La Marche 2008 (PMID 18597114) says 6–15%, and Beaudet 2007 (PMID 17479094) guesses that it will grow to 30–40% as the resolution of array CGH improves. Eubulides (talk) 17:43, 2 September 2008 (UTC)

[edit] Wall et al. on genome-wide search

PubMed reports the following new source, but it hasn't been published yet. Might be worth a look-see once it has been published.

Wall DP, Esteban FJ, Deluca TF et al. (2008). "Comparative analysis of neurological disorders focuses genome-wide search for autism genes". Genomics. doi:10.1016/j.ygeno.2008.09.015. PMID 18950700. 

Eubulides (talk) 06:36, 29 October 2008 (UTC)

"Epub ahead of print" is "published," just not in print. Usually, you can find a copy of the article on the journal's web site.68.46.183.96 (talk) 19:46, 19 November 2008 (UTC)
Yes, thanks for reminding me; the article was finally published on the journal's web site on November 12 (wow, that's quite a delay compared to PubMed). I'll take a look at it now.

[edit] Kumar and Christian on genetics of ASD

Here's a recent review that looks like it would be worthwhile, but I lack ready access to it.

Kumar RA, Christian SL (2009). "Genetics of autism spectrum disorders". Curr Neurol Neurosci Rep 9 (3): 188–97. PMID 19348707. 

Eubulides (talk) 20:52, 8 April 2009 (UTC)

[edit] Big addition to Reelin

In the \autism\ subsection of the reelin article yesterday a big chunk of text was added by a new user; I'm not savvy in the autism-related Reelin studies, and think that some newly added phrases should be cut from the reelin article as loosely related to the reelin itself (big head size etc.) Maybe some of them could be shifted here? If interested, take a look. --CopperKettle 14:09, 1 June 2009 (UTC)

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