Talk:Heritability of autism/Archive 1

"Mendelian" "model"

Hopelessly simplistic, as well as wrongly spelled. Best taken out and a discussion of linkage added, or just a pointer to an article on genetics. Midgley 22:05, 12 April 2006 (UTC)

Heritabilities

I removed the unjustified weakness on the heritabilities based on my expertise with estimating these. KimvdLinde 15:16, 15 April 2006 (UTC)

Heritability is only not Autism (causes) if it doesn't include the environmental hypotheses

Otherwise this is just yet another fork/duplicate. Midgley 19:34, 8 July 2006 (UTC)

Idiopathic autism?

That suggests that there are two (or more) sorts of autism, that caused by specifics and that for whcih no cause is known. Since tehre is no indication that we know a cause for even some autism that seems very like original research. Midgley 19:36, 8 July 2006 (UTC)

Candidate gene loci

There appears to have been a lot more text here that got thrown out with l33tminion's revision as of 11:38, 7 March 2006 -- probably accidentally. I'm not qualified to determine whether it should be restored to the article, so I'm putting it here for reference. --Collabi 22:17, 16 July 2006 (UTC)

• SLC25A12

This gene, located in chromosome 2q31, encodes the mitochondrial aspartate/glutamate carrier (AGC1). It has been found to have a significant linkage to autism in some studies [1][2] but linkage was not replicated in others [3].

• HOXA1 and HOXB1

Dr. Patricia Rodier [4] has identified a link between HOX genes and the development of the embryonic brain stem. In particular, two genes, HOXA1 and HOXB1, in transgenic 'knockout' mice, engineered so that these genes were absent from the genomes of the mice in question, exhibited very specific brain stem developmental differences from the norm, which were directly comparable to the brain stem differences discovered in a human brain stem originating from a diagnosed autistic patient [5].

Conciatori et al (2004) [6] has found an association of HOXA1 with increased head circumference. A number of studies have found no association with autism [7][8][9].

However, the possibility remains open that while single allelic variants of the HOXA1 gene are insufficient alone to trigger the developmental events in the embryo now associated with autistic spectrum conditions, Tischfield et al [10] published a paper which suggests that bexause HOXA1 is implicated in a wide range of developmental mechanisms, a model involving multiple allelic variants of HOXA1 in particular may provide useful insights into the heritability mechanisms involved. Additionally, Ingram et al [11] alighted upon additional possibilities in this arena. Transgenic mouse studies including Rossel & Capecchi [12] indicate that there is redundancy spread across HOX genes that complicate the issue, and that complex interactions between these genes could play a role in determining whether or not a person inheriting the requisite combinations manifests an autistic spectum condition - transgenic mice with mutations in both HOXA1 and HOXB1 exhibit far more profound developmental anomalies than those in which only one of the genes differs from the conserved 'norm'.

Note that in Rodier's original work, teratogens are considered to play a part in addition, and that the possibility remains open for a range of teratogens to interact with the mechanisms controlled by these genes unfavourably (this has already been demonstrated using valproic acid, a known teratogen, in the mouse model).

• PRKCB1

Philippi et al (2005) [13] has found a strong association between this gene and autism. This is a recent finding that needs to be replicated.

• FOXP2

The FOXP2 gene is of interest because it is known to be associated with developmental language and speech deficits. An association to autism appears to be elusive, nonetheless [14][15].

• UBE3A

The UBE3A gene has been associated with Angelman syndrome. Samaco et al (2005) [16] suggests there's reduced expression of UBE3A in autism, as is the case in Rett syndrome. In any case, it appears that the role of UBE3A is limited.

• Others

There is a large number of other candidate loci which either should be looked at or have been shown to be promising. Several genome-wide scans have been performed identifying markers across many chromosomes [17][18][19]. A few examples of loci that have been studied are the 17q21 region [20], the 3p24-26 locus [21], PTEN [22], 15q11-q13 [23], etc. Other possible candidates include:

• SLC6A2 (Social phobia)
• FMR1 (Fragile-X)
• 5-HT-1Dbeta (OCD)
• 7q11.23 (William's syndrome, language impairment)
• 4q34-35, 5q35.2-35.3, 17q25 (Tourette syndrome)
• 2q24.1-31.1 (Intelligence)
• 6p25.3-22.3 (Verbal IQ)
• 22q11.2 (Visio-Spatial IQ)

I'd like to know how come this was thrown out, and why. In the case of the HOXA1 and HOXB1 information I supplied, this is the subject of ongoing research backed by NIH funding in the USA - check the University of Rochester list of current grants for the list of NIH funding entries associated with Dr Rodier's work. I find it strange that research that is the subject of current NIH funding shceduled to continue until 2008 should have been deleted from this article. Can someone explain why? Calilasseia 21:07, 6 September 2006 (UTC)

If there was no edit summary it could be treated as vandalism, essentially. Neurodivergent 22:02, 6 September 2006 (UTC)

I've decided to replace the missing block of text. Epecially as it is replete with references to the relevant pieces of research, and therefore should not have been edited out in the first place. First of all, the block being replaced meets the verifiability critera (enough links to Scientific American and PubMed among others to satisfy even the most nit picking of critics) and it covers important research that is, in the case I've cited above (and almost certainly in the others) the subject of continuing research funded by government bodies such as the NIH in the United States, and the Medical Research Council here in the UK. If anyone wishes to remove it, STATE VALID REASONS FOR REMOVAL. Calilasseia 18:24, 8 September 2006 (UTC)

Autism text relocation

The Autism article is accruing a lot of material that is more relevant to the theme here and is thus getting very redundant. I have relocated the text here and and I am writing a synopsis there. Malangthon 01:39, 7 March 2007 (UTC)

Ritvo 1989.

In response to OTRS 2006090110007688, and before finding this page, I found [24]: "Siblings born after one autistic child were 215 times more likely to have autism than siblings of nonautistic children", "The probability of a recurrence in children born after an autistic girl is 14.5 percent, while a recurrence after an autistic boy is 7 percent". Is this now regarded as too high? Was the variant net cast wider? -- Jeandré, 2006-09-05t12:37z

Please clarify...

This is confusing:

"For example, it would appear that about 40% of diagnosed individuals originally had a 50/50 chance of being considered high functioning. About 4% to 10% had a 50/50 chance of escaping a diagnosis altogether."

At least to the lay person this seems to say that 4% to 10% of those were diagnosed -- were not diagnosed!

(This makes no sense to me.)

There must be a better way to phrase whatever was meant here.

- ef

"Popular among parents?"

Whoever characterized the thimerosal issue as "popular among parents" should think long and hard about the role of parents in the health of their children. --Leifern 20:25, 5 February 2007 (UTC)

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)

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)

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:

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.

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)

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)

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)

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):

• Sutcliffe JS (2008). "Insights into the pathogenesis of autism". Science. 321 (5886): 208–9. doi:10.1126/science.1160555.

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

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)

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)

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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

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. — Preceding unsigned comment added by Eubulides (talk • contribs) 19:50, 19 November 2008 (UTC)

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)

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)

Page loading efficiency and style

This page takes a long time to load, and part of this is due to the use of the standard Wikipedia citation templates such as {{cite journal}}. Recently developed faster & smaller templates (such as {{vcite journal}}) should make the page a lot smaller and faster to load, and I'd like to try them out here. Assuming they work well here, we can use them in other autism-related pages. Eubulides (talk) 20:25, 22 January 2010 (UTC) PS. I just tried it out, and the current version generates 260,536 bytes of HTML, 70% bigger than the proposed version (which generates 153,143 bytes of HTML); in one test the current version takes about 16 seconds to load while editing, about 75% longer than the 9 seconds of the proposed version (the timings are variable but this sort of improvement is common). Eubulides (talk) 20:46, 22 January 2010 (UTC)

Jay Joseph: Missing Gene

I found the following line and thought it needed a "Who?" tag but apparently the reference was in the Wiki but just didn't link properly.

"One critic of the pre-2006 twin studies said that they were too small and their results can be plausibly explained on non-genetic ground"

According to the wiki page source. This refers to Jay Joseph's "The Missing Gene" a book by someone who is not a geneticist refuting (or attempting to) the idea of a genetic basis for various disorders. I think this line is misleading, Mr. Joseph does not actually refer to these studies individually but rather makes blanket arguments against various tests for heritability like family studies and twin studies. That said, his argument against twin studies is based on the idea that MZ twins tend to spend more time together and eat similarly than DZ twins and argues that it is probable (although it's questionable if this argument is made) that nutritional and environmental differences would be mistakenly correlated as genetic. The study he cites falcizia & norton 1994 looked at twins aged 9 to 18. So while this may well be good criticism for other twin studies it seems way off for a disease that has far more often than not presented by 36 months.

He also cites the failure to find commonalities in all genome wide searches. Which he attributes to Blaxill. Blaxill is also not a professional in the field and is at best somewhat biased. —Preceding unsigned comment added by 205.211.168.16 (talk) 22:11, 8 July 2010 (UTC)

Anyway I'm not sure what they best course of action is here but to me the current line implies that the author provided applicable criticism about the specific studies mentioned above (i.e. the MZ/DZ twin studies) which is at best debatable. —Preceding unsigned comment added by 205.211.168.16 (talk) 22:14, 8 July 2010 (UTC)

Mitochondria

What about sources on mitochondrial malfunction and transmission of mitochondrial DNA via the egg? 129.112.109.253 (talk) 22:12, 13 December 2010 (UTC)

I mentioned this below: https://secure.wikimedia.org/wikipedia/en/wiki/Talk:Heritability_of_autism#Neanderthal_Admixture_Hypothesis

Slartibartfastibast (talk) 21:47, 9 June 2011 (UTC)

Neanderthal Admixture Hypothesis

My only request is that you read before you delete:

The Journal of Evolutionary Psychology just published a paper that supports the hypothesis that the confirmed neanderthal admixture event(s) provided cognitive variations that were subsequently selected for, sometimes causing a locus of deleterious recombinations in the genomes of children with parents who selected one another for those characteristics: http://www.epjournal.net/filestore/EP09207238.pdf

• "People on the autism spectrum are conceptualized here as ecologically competent individuals that could have been adept at learning and implementing hunting and gathering skills in the ancestral environment."
• "The autism continuum could represent a remnant of genetic introgression that took place before humans were the lone species in our genus. Perhaps some of the genes for autism evolved not in our direct ancestral line but in a solitary subspecies which later merged genetically with our line of descent through gene flow."
• "Many of the behavioral and cognitive tendencies that autistic individuals exhibit are viewed here as adaptations that would have complemented a solitary lifestyle. For example, the obsessive, repetitive and systemizing tendencies in autism, which can be mistakenly applied toward activities such as block stacking today, may have been focused by hunger and thirst toward successful food procurement in the ancestral past. Both solitary mammals and autistic individuals are low on measures of gregariousness, socialization, direct gazing, eye contact, facial expression, facial recognition, emotional engagement, affiliative need and other social behaviors. The evolution of the neurological tendencies in solitary species that predispose them toward being introverted and reclusive may hold important clues for the evolution of the autism spectrum and the natural selection of autism genes."
• "This article emphasizes that individuals on the autism spectrum may have only been partially solitary, that natural selection may have only favored subclinical autistic traits and that the most severe cases of autism may be due to assortative mating. "
• "Unfortunately, the genetics, molecular biology and neuroscience of autism are still, relative to many other neurological disorders, shrouded with uncertainty due to their highly complex nature (O’Roak and State, 2008)."
• "A portion of this complexity and uncertainty arises from the relatively large number of distinct susceptibility genes that have been identified, many of which can be completely absent even in pronounced autism (Freitag, 2007). This genetic heterogeneity may be responsible for the clinical heterogeneity..."
• "1. isolated pockets of humans can remain reproductively insulated for long enough to evolve discrepant ecological strategies; 2. such populations can quickly (less than 40,000 years in the South American and Asian pygmies; Cavalli-Sforza, 1986) develop features that vary markedly from the norm; 3. these traits can involve multiple genes at different loci; and 4. interbreeding can result in either continuous or polymorphic variation in subsequent generations. It is interesting to note that, as these indigenous people become assimilated into other gene pools, the genes for short stature will persist and may affect phenotypic variability in sporadic and unpredictable ways for a long time to come."
• "Like other polygenic, continuous traits, the mutations responsible for autism could have been maintained by “environmental heterogeneity,” a form of balancing selection. In other words, the genes responsible for autism may have remained in our gene pool because as social-environmental conditions fluctuated in the past, discrepant genetic polymorphisms, or “multiple alternate alleles,” were favored."

Here are some peer reviewed sources that imply a link between the genes garnered via neanderthal admixture and the genes that code for ASDs:

• Brain development after birth differs between Neanderthals and modern humans (2010, Max Planck Institute for Evolutionary Anthropology) B]

"The development of cognitive abilities during individual growth is linked to the maturation of the underlying neural circuitry: in humans, major internal brain reorganization has been documented until adolescence, and even subtle alterations of pre- and perinatal brain development have been linked to changes of the neural wiring pattern that affect behavior and cognition [9]. The uniquely modern human pattern of early brain development is particularly interesting in the light of the recent breakthroughs in the Neanderthal genome project [10], which identified genes relevant to cognition that are derived in living humans. We speculate that a shift away from the ancestral pattern of brain development occurring in early Homo sapiens underlies brain reorganization and that the associated cognitive differences made this growth pattern a target for positive selection in modern humans."

• A Draft Sequence of the Neandertal Genome

"Mutations in CADPS2 have been implicated in autism (67), as have mutations in AUTS2 (68)."

• Autism, the Integrations of ‘Difference’ and the Origins of Modern Human Behaviour (McDonald Institute for Archaeological Research)

The fact that the male side of the admixture(s) was/were strictly neanderthal would mean that we share none of their mtDNA. This explains the lack of mtDNA abnormality and the existence of mitochondrial dysfunction in people with ASDs: http://www.biomedcentral.com/1471-2350/12/50

• "the frequent observation of concomitant mitochondrial dysfunction and ASD could be due to nuclear factors influencing mitochondrion functions or to a more complex interplay between the nucleus and the mitochondrion/mtDNA."

The neanderthal haplotype described in this 2011 paper is x-linked: http://mbe.oxfordjournals.org/content/early/2011/01/25/molbev.msr024.full.pdf+html

The abstract finishes by saying: "It indicates a very early admixture between expanding African migrants and Neandertals prior to or very early on the route of the out-of-Africa expansion that led to the successful colonization of the planet." [On a side note: This could also explain the unique, cyclical pattern of brutal invasion, cultural assimilation, and intermarriage that is so common in the written history of human civilization. Evidence of mostly patrilineal migrations among early AMHs is just coming out: http://www.pnas.org/content/early/2011/05/24/1100723108 "Ancient DNA reveals male diffusion through the Neolithic Mediterranean route" (May 2, 2011)]

More evidence is cited in this wrongplanet thread: http://www.wrongplanet.net/postp3696657.html#3696657 — Preceding unsigned comment added by Slartibartfastibast (talk • contribs) 21:46, 9 June 2011 (UTC)

This is the same content as is on talk:Asperger syndrome. I think it is best to keep the discussion there where it may attract more viewers, as this article is fairly low traffic. —Soap— 21:53, 9 June 2011 (UTC)

It has received no attention there. I copied it here in the hopes that someone would respond. Why has nobody else analyzed this or given the go-ahead to put it in the main article? — Preceding unsigned comment added by Slartibartfastibast (talk • contribs) 22:07, 9 June 2011 (UTC)

An important distinction

The following comment is from the recently published Nature article "Brain cell genomes show their individuality"

"One of the conclusions of studies like this - and the Bruder et al study a few years ago on somatic copy number mosaicism - is that twin studies are not an accurate measure of the geneticness of any given disorder or trait. Nature recently published a set of features on autism for example which repeated the well known claim that twin studies show that autism has an environmental component. They don't. What they show is that there is a component that isn't inherited. That component could be environmental but as this result and others show it could also be genetic. Indeed some studies have suggested that as much as 90% of autism may be genetic and yet, many years ago, Nature had a feature quoting Susan Folstein as claiming that roughly 10% of people with autism showed evidence for mosaicism, which wouldn't be picked up in a twin study despite being genetic. Its possible therefore that autism may be much more strongly genetic that hinted at by twin studies." -Michael Chisnall (November 16, 2011 04:30 AM)

Slartibartfastibast (talk) 01:22, 17 November 2011 (UTC)

Epidemiology of Autism?

If someone has the data, it would be great to add a section or Wiki article re the worldwide incidence rate of autism, as has been done w/schizophrenia here: http://en.wikipedia.org/wiki/Epidemiology_of_schizophrenia

Phantom in ca (talk) 05:42, 5 December 2011 (UTC)

Syndromic autism

• Benvenuto A, Manzi B, Alessandrelli R, Galasso C, Curatolo P (2009). "Recent advances in the pathogenesis of syndromic autisms". Int J Pediatr. 2009: 198736. doi:10.1155/2009/198736. PMC 2778501. PMID 19946417.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)

With two syndromes, Fragile-X syndrome and Tuberous sclerosis, counting for between 5 and 9% of all ASD patients (according to the above), syndromal cases of autism deserve greater prominence in the article (and Causes of autism, etc). This would also help emphasise that there are some genetic conditions that we know are strongly associated with autism, not just some vague increase in risk waiting for an environmental factor to occur. Colin°^Talk 21:52, 2 January 2010 (UTC)

I added a brief note to this article. The article is currently quite dated (most of the chromosome stuff is about 4 or 5 years old now, and needs to be drastically revised or thrown out), but it'll take some work to fix it. Eubulides (talk) 06:25, 3 January 2010 (UTC)

Sakai et al. 2011 Protein interactome reveals converging molecular pathways among autism disorders. This paper especially, as well as other independent lines of evidence, firmly establishes syndromic forms of autism as central to the autism risk factors genes. --Arm42 (talk) 04:49, 20 December 2011 (UTC) User: arm42, 19 December 2011.

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Autism Genome Project change

Autism speaks has information about the Autism Genome Project refer to the Autism Genetic Resource Exchange. I think that the AGRE has replaced the AGP and this needs to be reflected in the article. More could be written about the AGRE as well. --FUNKAMATIC ~talk 19:56, 25 May 2013 (UTC)

Limit to the percentage of genetically explained autism?

"traceable to a genetic cause may grow to 30–40%" -- This undefended statement seems to predict that only 30 to 40% of autism will ever be explained through genetic causes (often called "risk factors"). This should be reworded, since there is no basis offered for an upper limit to the percentage. The dangers of over-interpretation of GWA studies are well documented in the article and is not being questioned here. — Preceding unsigned comment added by Arm42 (talk • contribs) 05:01, 20 December 2011 (UTC)

'agreed.' I'll see if I can find the time to do it later if no one else gets to it.--FUNKAMATIC ~talk 19:58, 25 May 2013 (UTC)

Discussion of non genetic causes is appropriate

Since no clear number is stated for percentage of autism cases which are heritable, it seems appropriate to mention the approximate percentages of non-heritable causes.

Maternal antibodies, Maternal immune activation, auto antibodies, fraternal twin concordance being higher than sibling concordance, and the study from Stanford attributing much greater than 10% to non genetic causes.

All this could be included. — Preceding unsigned comment added by 107.198.86.118 (talk) 01:25, 26 August 2013 (UTC)

Ethnic Celts and autism

Are ethnic cetlic people more likely to have autism? The reason why the vaccine-autism link is cited by celtic people is because amish people have a very low rate of autism and amish are Germanic people. All the people who claim vaccines cause autism are ethnically celtic so celtic people seem to have autism at a higher rate that Germanic people. Why do not scientist split Germanic people from celtic people in their studies? — Preceding unsigned comment added by 50.103.134.70 (talk) 01:45, 25 March 2014 (UTC)

Heritability Explanation

This page incorrectly interprets the meaning of heritability estimates. From the page: "The heritability of autism is the proportion of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic." This is exactly wrong, as the heritability page that the sentence link to clearly explains: "Heritability measures the fraction of phenotype variability that can be attributed to genetic variation. This is not the same as saying that this fraction of an individual phenotype is caused by genetics." And later on general heritability page "Heritability describes the population, not individuals within that population. For example, It is incorrect to say that since the heritability of a personality trait is about .6, that means that 60% of your personality is inherited from your parents and 40% comes from the environment." A more accurate wording would be along the lines of: "The heritability of autism estimates the how much of the variability in autistic and non-autistic traits within a particular population stems from variation in the population's underlying genetic make-up and how much stems from environmental variation. Heritability varies between populations and environments and does not provide a measure of how much a particular person's symptoms (or lack thereof) are caused by their genes." — Preceding unsigned comment added by 76.91.199.119 (talk) 20:03, 1 April 2014 (UTC)

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