Nature has published a paper on the genetics of autism which we report here . Over the coming days and weeks, we will post updates on this important story and links to sources of further information

The story so far

• Alleged conflict of interest

• North American press coverage and blogs

• Appeal for blood samples

• Public policy implications

• An executive summary from PZ Myers

• The importance of copy number variations

• Oxford researchers speak

• British press coverage

• 'A great deal more research to be done'

• Autism is not a single-gene disorder

• Is there evidence for environmental factors?

• Genes involved in brain function

Alleged conflict of interest

Tuesday June 15, 11.25am: At ScienceBlogs, Orac has posted a response to John Stone's article on alleged conflicts of interest on the Age of Autism blog.

Orac points out that, just because the senior author of the Nature paper, Stephen Scherer, has a professorship that is endowed by the drug company GlaxoSmithKline, it does not automatically imply a conflict of interest or bias in his research. To create an endowed chair, says Orac, a company or wealthy donor gives a university a lot of money, and the university sets up the endowed chair using that money. Interest and dividends from the fund are then put at the disposal of the holder of the chair to do research and scholarship as he or she sees fit. This model is desirable because endowed chairs give researchers a reliable source of money without needing to write grant proposals all the time. Orac continues:



Once an endowed chair is set up, the donor usually has no say over who gets the chair or how the money for the chair is spent. Claiming that Professor Scherer's holding the GSK chair at his institution is an insurmountable COI [conflict of interest] that needed to be reported is, quite simply, ridiculous to anyone in academia who knows what an endowed chair is. Clearly, Mr. Stone does not, although one commenter going by the 'nym of Werdna does try to set Mr. Stone straight. It's a rare thing indeed on AoA [Age of Autism] for a commenter to take a blogger to task like that, something that usually only happens when an AoA blogger makes a mistake too egregious even for some of the less nutty AoA readers.

It's also well worth reading Orac's masterful description of the Nature research itself. There's lots of technical detail here but worth persevering with if you're interested in getting a handle on the complex genetics behind autism.

5.47pm: Blogger John Stone alleges that the senior author of the Nature study had a "competing interest" that was not clearly stated in the paper.

Writing on the blog Age of Autism, Stone says Stephen Scherer's position as GlaxoSmithKline-CIHR Pathfinder Chair in Genetics and Genomics at the Hospital for Sick Children and University of Toronto was "tucked away" in the acknowledgements for the paper rather than being declared prominently as a competing interest.

GlaxoSmithKline manufactures an MMR vaccine called Priorix.

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North American press coverage and blogs

Monday 12.14pm: Two more excellent US write-ups of the research, in Time and on Yahoo Health.

The Yahoo Health story concludes:

"What the study does not answer is how the genetic changes occur. Genes can be altered by the environment and the age of the parents has been linked with autism in some studies. Some advocacy groups maintain that vaccines can cause autism, although many studies have ruled this out and a British researcher whose work gave the vaccine movement its impetus has had his study and medical license withdrawn."

A Canadian blogger, "Facing autism in New Brunswick", takes up this theme with a call for more research into environmental triggers of the condition:

"Over the past two decades funding for autism research has been provided overwhelmingly in favor of genetic autism research. This major new study which is prompting gleeful headlines around the world actually tells us that there is no common genetic cause of autism, that there are many specific genetic mutations involved with autism. As reported on CTV News which interviewed Dr Stephen Scherer, one of the lead researchers on the project , the study itself did not identify all the genetic factors involved with autism disorders and does not begin to identify possible environmental triggers."

The blogger wants to know how the genetic changes occur, and what the environmental triggers might be for those with a genetic susceptibility.

"As far as I can tell from reading various reports the study does not rule out ANY possible environmental causes or triggers of autism or of the genetic changes reported in the study. If anything the study appears to indicate the need for research of environmental triggers to begin in earnest after decades of intentional neglect by those with responsibility for funding autism research."

Thanks to Dorothy Bishop, professor of developmental neuropsychology at the University of Oxford, for bringing these articles to our attention.

8.19pm: More coverage from the US, where parents and patient groups have blamed mercury in vaccines for the rise in diagnosed cases of autism, according to The Palm Beach Post. The article continues:

"The majority of scientists say the assertion has been debunked and that vaccines play no role in autism, but some parents and patient groups contend it's true."

Meanwhile, in a personal piece based on her experience of having a brother diagnosed with the condition, Grace Boyle at the Independent says:

"To suggest that these [genetic] variations represent an illness that can be treated sits uncomfortably with me, and I'm sure with many others."

The blog LBRB (Left Brain, Right Brain – autism news, science and opinion) has an interview with one of the researchers, Stephen Scherer:

"I am always frustrated when I hear at the end of most news stories … 'and we don't know what can cause autism'. Data from the past few years including our new study show alterations in genes can cause autism. We have not found all of the genes yet, and not all autism cases can be accounted for (the genetics can be complex) but genes can cause autism."

He goes on:

"I think one of the most important impacts of the study is the design itself ... CNV [Copy Number Variation] studies are still quite tricky to do and the data has to be of the highest quality to make sense of it. I think our study on autism will set the standard for all other studies going forward, so they should follow it."

6.49pm: Ruth Francis, head of press at Nature Publishing Group, also gives the thumbs-up to Scientific American's reporting of the findings. The point about the research explaining the genetic basis of only 3% of autism cases is pressed home.

Scientific American quotes Rita Cantor of the David Geffen School of Medicine at the University of California, Los Angeles:



Cantor says a study 10 times bigger – sampling 10,000 children with autism and as many controls – would be required to see if the results replicate in a larger population as well as uncover new, rare genetic variations, which are almost certain to emerge.

Whole genome sequencing will also be important to pinpoint other kinds of genetic variation involved in autism.

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Appeal for blood samples

6.19pm: Several US blog and news sites reported the Nature paper. Of particular note is Nancy Shute's blog for USNews.com in which she passes on an appeal for American parents of children with autism to come forward for genetic testing through the Interactive Autism Network.

Stanley Nelson, a geneticist at the University of California-Los Angeles who is involved in the online project, emailed her about the Nature paper saying:

"This work is grossly inadequate, even though it reflects about 15 to 20 years of sample collection, tens of millions [of dollars] in molecular testing, and analytical effort."

The study explained the genetic basis of only 3% of diagnosed cases of autism, he said.

It turns out Nelson has no quibbles with the research itself but believes that blood samples from many, many more patients are needed to get the complete picture.

According to Nelson it cost the Autism Genome Project more than $4,000 (around £2,800) to test each family, including a home visit by a trained researcher. Otherwise families had to live near a major research institution where they could present themselves.

The Interactive Autism Network claims its online application form and network of 1,600 testing centres across the US can cut that to around $100 (£70) per DNA sample.

The database used by the Nature researchers, the Autism Genetic Resource Exchange, has samples from about 10,000 people with autism. Nelson wants to boost that number to 300,000.

That's an audacious goal, says Shute, "but Nelson thinks it's the only way scientists will be able to crack the mystery of autism."

Elsewhere in the US media, Saundra Young of CNN provides a good roundup of the research and reports that the Autism Genome Project is currently analysing a further 1,500 families. There's also a thorough write-up by Katharine Harmon at Scientific American.

Our thanks to blogger Heather Doran at the Institute of Medical Sciences, University of Aberdeen, for passing on these US links.

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12.17pm: NHS Choices provides a very useful explainer on the new research for patients and parents. Thanks to @cebmblog for directing us to the article.

Public policy implications

11.55am: This may be a good time to mention that we have set up a Twitter account @StoryTracker both to notify followers about the latest updates to our science story trackers and to receive new nuggets of information.

@xmalik, who is a clerk on the House of Commons science and technology committee in the UK, has tweeted that there is a POST document from February 2008 summarising the public policy implications of the discovery that autism is more prevalent than was previously recognised.

(POST is a parliamentary office that provides "independent and balanced analysis of public policy issues that have a basis in science and technology".)

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An executive summary from PZ Myers

Friday 11.36am: Dorothy Bishop, professor of developmental neuropsychology at Oxford University, has sent us a link to PZ Myers' excellent blog on the new research. Myers provides an "executive summary" of the paper:

A large study of almost a thousand autistic individuals for genetic variations that make them different from control individuals has found that Autism Spectrum Disorder has many different genetic causes: there isn't one single gene responsible for ASD, but a constellation of hundreds, each with the potential to affect the development of the brain and cause the symptoms of autism. They don't know exactly how each of these genes contributes to the disorder, but they have found that many of them are involved in growth and cell communication and the formation of synapses in the brain. The bottom line is that there are many different ways to cause the symptoms of autism, and it's a mistake to try to pin it all on single, simple causes. Any hope for amelioration lies in understanding the general functional processes that are disrupted by mutations in various pathways.

So autism has every appearance of being hundreds of diseases, and the genetic cause in every individual is unique. Don't despair, says Myers, this is just the start. "Although there are many genes involved, we can try to ask what all of them have in common functionally."

Here's a first stab at puzzling out what these genes do. The genes that have been identified as being deficient in ASD individuals are mapped out by known functions, and what jumps out at you is that the hundreds of specific genes fall into a smaller number of functional categories. Many of them cluster in a few functional roles: cell proliferation (genes that affect the number of cells in a tissues) and cell projection (particularly important in neurons, where cells will extend long processes that project into target regions), and a specific class of cell signaling molecules, RAS-GTPases, which are involved in how cells communicate with one another and are particularly important in synapses, or the linkages between neurons.

Cautiously, Myers concludes that this commonality gives some "hints of hope for future treatment".

To those still seeking an environmental cause for autism in the early life of children, he has this to say:

One fact is so obvious that it's unfortunate I have to mention it: no external agent, such as a vaccine, can generate a consistent pattern of duplication and deletions in an affected individual's cells.

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The importance of copy number variations

Thursday 10 June, 7.15pm: At 80Beats, the Discover blog news aggregator, writers make it clearer how some of the variants seen in the autistic children came about – not all are inherited:

For this study, researchers at the international Autism Genome Project wanted a closer, more detailed picture of the over 100 genes commonly linked to autism. They looked for rare variants – small deletions or additions to the DNA sequences that make up these genes. They found that people with autism had a higher number of these variants than those without the disorder, and that some of these DNA differences were not inherited. That means these DNA changes occurred either in the egg cell, sperm, or in the developing embryo.

At New Scientist's Short Sharp Science blog, Celeste Biever notes how copy number variations (CNVs) are becoming an important area of study for genetics researchers:

CNVs are increasingly being implicated in a range of conditions, from obesity to schizophrenia. But it's not the first time they have been implicated in autism. In 2007, a team led by Jonathan Sebat of Cold Spring Harbor Laboratory on Long Island, New York, found that they were 10 times as common in autistic children as in other children - based on a study that looked at 118 families that each had one autistic child. More recently the prevalence of CNVs in people with autism has been used to support a theory that suggests autism and schizophrenia are at opposite ends of a common spectrum, or two sides of the same coin.

Amanda Gardner at Bloomberg Business Week highlights the connection between autism and other learning disorders as outlined by the researchers. Quoting Stephen Scherer of the The Hospital for Sick Children and University of Toronto, and Andy Shih, vice president of scientific affairs at Autism Speaks, the charity which part-funded the work:

"About 6% of these occur as new CNVs in autistic individuals but the vast majority are rare, inherited CNVs," Scherer explained. "With autism, there's a higher likelihood of having CNVs in their genes, especially genes related to intellectual disability," Shih stated. About 40% to 50% of kids with autism also have intellectual disabilities, Scherer pointed out. There were also commonalities with other disorders, including schizophrenia, Shih said.

Science Now explains that "just over 5% of those affected had at least one 'de novo' copy number variant that had appeared in the sperm or egg cell forming the embryo, or spontaneously in the fertilised egg."

There was also more on the function of the genes affected by the copy number variations:

That said, the team found that genes deleted in autistic patients tended to perform similar tasks. Many were involved in aspects of cell proliferation, such as organ formation. A number participated in development of the central nervous system and others in maintaining the cytoskeleton, which protects the cell and helps it move.

On the BBC, Pallab Ghosh quotes Anthony Monaco on the possibility of tests in British hospitals:

According to Professor Monaco: "The idea is to track these genes in their families and see if we can offer genetic counselling and what information we can offer the patient. If we can show the efficacy of that in the clinical care of the patients then we can push for it into genetic testing in the NHS."

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Oxford researchers speak

Thursday 10 June, 7pm: The University of Oxford researchers involved have been speaking to BBC World Service Newshour - Anthony Monaco and a parent of children with autism-spectrum disorder talked about the implications.

A BBC Oxford interview illustrates just how excited the scientists involved in the autism study are with their results.

Thanks to @jpawood in the University of Oxford press office for those links. Talking of which, here's the Oxford press release on the research.

For reference, here are the press releases from some of the main institutions involved in the study:



DNA scan for familial autism finds variants that disrupt gene activity in autistic kids (University of California, Los Angeles)

TCD researchers discover new autism genes as part of major international research project (Trinity College Dublin)

New genetic findings expected to accelerate autism testing and development of treatments (The Hospital for Sick Children, University of Toronto)

New autism genes discovered: Autism Speaks and the world's leading autism experts announce phase 2 results of the Autism Genome Project (Autism Speaks)

Also, here is Nature's press release for the paper:



Genetics: The roots of autism (AOP)

DOI: 10.1038/nature09146 This week in Nature, Stephen Scherer and the Autism Genome Project Consortium describe the results of a genetic analysis of the largest assemblage of families with autism spectrum disorder. The autism spectrum disorders (ASDs) are a group of conditions characterized by highly repetitive behaviour, severely restricted interests, and problems with social interactions and communication. Although ASDs are known to be highly heritable, geneticists have struggled to home in on the precise genetic elements responsible. The authors looked for copy number variants (CNVs) — segments of DNA for which the copy number differs between individual genomes — across the genomes of nearly 1,000 ASD individuals and around 1,200 healthy people. Their comparison shows that ASD sufferers carry a greater number of rare CNVs, both inherited and those that have arisen for the first time in the ASD sufferers. These variants frequently involve coding portions of the genome. The study implicates many novel genes as ASD candidates. For example, in people with an ASD, CNVs disrupt sets of genes involved in cellular proliferation, projection and motility, and GTPase/Ras signalling pathways.

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British press coverage

Thursday June 10, 1:00pm: Interesting to see how this story has been covered in different places. The Nature news blog applies its trademark clarity on who did what and what they found and contains some inteersting detail on the actual variants uncovered in the research, such as "one region of the X-chromosome, called the DDX53-PTCHD1 locus, were associated with a three-fold higher risk of autism spectrum disorder."

Mark Henderson in The Times raises the possibility of genetic tests for autism. Over at The Independent the main story by science editor Steve Connor claims that the latest Nature research is the "first significant link between autism and DNA" while health editor Jeremy Laurence argues that the "biggest puzzle about autism is the huge rise in cases, up 12-fold among children in the past 30 years, according to some estimates". Not sure about the premise of the Indy's news story, especially given that several gene variants were implicated in autism barely a year ago and the results published in Nature and the Annals of Human Genetics. See the Guardian, Times and WebMD.

At the Telegraph, Richard Alleyne blames autism on "rogue genes". The Mirror also a short report.

By the way, several commenters seem concerned at the implications of the research, asking why was it done and wondering whether it is just a way to brand autism as a disease that can and should be eliminated. For anyone thinking that, I'd suggest you read Charlotte Moore's article in the Guardian, explaining what the Nature study means to her.

Next update will include bloggers' reactions so far, so send me any links you think are worth including. So far I quite like Discover for its impressive detail.

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'A great deal more research to be done'

Wednesday 8.33pm: Gina Gómez de la Cuesta, action research leader at The National Autistic Society, says: "This study furthers our understanding of genetic variation in autism, however there is a great deal more research to be done. Research into autism is constantly evolving but the exact causes are as yet still unknown. The difficulty of establishing gene involvement is compounded by the interaction of genes with the environment. Genetic testing for autism is still a long way off, given that autism is so complex. Whilst it is very important that research continues, it is also crucial that those living with the condition have access to appropriate advice and information, as the right support at the right time can make an enormous difference to people's lives."

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Autism is not a single-gene disorder

8.29pm: Anthony Monaco, a geneticist at the University of Oxford, re-iterated Gallagher's point by saying that the genetic picture of autism was too complex to make meaningful predictions right now.

"One can only offer, when we have a lot more data, an understanding of the probability of an outcome given you've inherited a CNV. It's not like cystic fibrosis or muscular dystrophy or other single-gene disorders where one can say with a lot more certainty that if you have a mutation in that gene then a pre-natal diagnostic test can be done and you can predict with fair certainty that the foetus does or does not have the mutation and will probably get the disorder. Here we're talking about low probabilities and risks and that will be the big issue with pre-natal testing and we won't be able to think about this until we gather a lot more information. Even with all that, it may be difficult to offer the certainty a person wants from a pre-natal test."

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8.24pm: What about genetic tests?

"Of course parents are going to rush out and want to get the tests done," said Louise Gallagher, clinical senior lecturer in psychiatry at Trinity College Dublin. But she warned that DNA microarrays – the technology needed to test for the autism gene variants – are not yet widely available in hospitals.

In any case, no one knows enough yet to be certain about the implications of having a certain set of genetic variations. "However, in future as we know more about the role of CNVs in contributing to autism and how they influence the progress and course of the disorder over the lifetime of the individual, the more [parents] will be able to get clinical information about their child's condition."

Is there evidence for environmental factors?

8.15pm: Scherer adds: "If you look at studies published to date, the most convincing finding of an aetiologic role in autism comes up with genetics. There've been estimates from numerous studies around the world from the last 20 years that 70-95% of autism has some genetic contribution ... With the rare CNVs, we can account for upwards of 10-15% of the genes involved now. There might be others that we have not yet detected. And certainly some of these genes may be influenced by environment. As far as I'm aware, through epidemiological studies, there's no [evidence of] strong influence from these other [environmental] factors yet."

8.08pm: Geri Dawson of Autism Speaks, a charity that helped to fund the research, addressed the question of environmental factors in autism. "We do believe that environmental factors play a role in autism," she said. "We don't yet understand the role of these factors so currently scientists are exploring a wide range of these factors to understand how they might interact with underlying genetic susceptibility."

For anyone worried about the effect of vaccines, she said there "really is no strong evidence that vaccines play a role in the aetiology of autism. This study really points out the strong influence of genetics. At the same time, research is continuing to explore a wide range of environmental factors that may then interact with genetic susceptibility. Currently there is no evidence that vaccines are one of those aetiological factors."

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Genes involved in brain function

7.33pm: Stephen Scherer of the Hospital for Sick Children in Toronto, Canada, said the study starts to tie together the genes they have identified with biological pathways and networks. "They seem to be involved in how the brain functions," he said. "Knowing these autism genes are linked, we can begin to develop rationally derived therapies to target the common pathways involved for the very first time."

For example, some of the genes implicated in the latest research are known to be involved in both neural cell development and signalling pathways.

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Story summary

In the largest study ever to look at the genetics of autism, scientists have identified rare genetic variations that were 20% more frequent in children with autism than in children without the disorder. These so-called "copy number variations" (CNV), which can be missing chunks or extra copies of DNA in and around the genes, occur in fewer than one in 100 people in the general population.

In the study, scientists compared the incidence of these rare CNVs in 996 people with autism spectrum disorders and in 1,287 unaffected people, all with European ancestry. The results, published today in Nature, showed that some of the CNVs were inherited while others were found in children but not in their parents.

Read the Nature research in full.

To submit suggestions for updates to this story tracker, please email guardianscience@gmail.com putting "Autism story tracker" in the subject line.

Here are some sources of further information for parents about autism on theguardian.com

Your autism questions answered – a handy resource for parents

Summary

What is it?

What are the symptoms?

How common is it?

What will happen to my child?

How do doctors diagnose it?

Questions to ask

What treatments work?

Autism spectrum disorder

Medical causes of autism

MMR vaccine and autism

Recent Guardian news stories related to autism

Andrew Wakefield struck off register by General Medical Council

Lancet retracts 'utterly false' MMR paper

Autism just as common in adults, so MMR jab is off the hook

Scientists find genetic clues to how autism can develop

Autistic traits linked to high levels of testosterone in the womb

For a complete list of Guardian articles on autism go to http://www.theguardian.com/lifeandstyle/autism

