The genetics of autism

I don't often venture into the fray whereby the misinformed continue to insist that thimerosal-containing vaccines cause autistic spectrum disorders when all evidence to date has led the scientific community to reject this hypothesis. However, recent stories on celebrities, namely Jenny McCarthy and Donald Trump, spouting forth about vaccines and autism led me to read with great interest a superb piece of science journalism by Ashley Pettus in the Jan-Feb 2008 issue of Harvard Magazine entitled, "A Spectrum of Disorders: The urgent search to understand the biological basis of autism."

In this well-research, four-page article written for general audiences, Pettus gives the antivaxers the one paragraph that the topic deserves:

Many parents became convinced that the escalating numbers of cases stemmed from exposure to thimerosal, a mercury-based preservative used in childhood vaccines. Another theory linked the measles/mumps/rubella (MMR) vaccine, in particular, to the onset of autistic symptoms. Numerous epidemiological studies have failed to substantiate these claims, and in 2004 the Institute of Medicine of the National Academies found no causal relationship between either mercury or MMR vaccine and autism.

After a concise and informative history of autism and Asperger's Disorder, Pettus instead spends the bulk of the article on the area where autism advocates should be registering their support: the genetic variation, usually spontaneous and not heritable, that underlying the spectrum of disorders.

A 1977 study of twins provided the first evidence of a genetic basis for autism. If one twin had the disorder, the other was far more likely to have it if he or she was identical rather than fraternal. (Because identical twins share their entire DNA, while fraternal twins share only half on average, a disease that tends to co-occur in identical pairs indicates genetic influence.) The discovery helped undermine the prevailing psychoanalytic theories that blamed autism on bad parenting and, in particular, on cold, unaffectionate, "refrigerator" mothers.

What has emerged from subsequent work is the autism and related disorders are complex, multigenic syndromes that require a multidisciplinary approach to solve:

"Autism is a problem that no one person or discipline can figure out alone," explains James Gusella, Bullard professor of neurogenetics and director of the Center for Human Genetic Research at Massachusetts General Hospital (MGH). Gusella chairs the executive committee of the Boston Autism Consortium, a largely privately funded initiative that began in 2005 to take advantage of the wealth of expertise, technological resources, and patient databases concentrated in the area. The consortium brings together more than 50 researchers from Harvard, MIT, the Broad Institute, MGH, Children's Hospital, Boston University, Beth Israel Deaconess Medical Center, and Tufts University to tackle different aspects of the disease cycle and to share results.

Understanding the true molecular and cellular basis of autism and early neuronal plasticity is already leading to some therapies, such as Applied Behavioral Analysis, that may help offset aberrant synaptic connections in spectrum disorders.

Note the key descriptor of the Boston Autism Consortium above: "a largely privately funded initiative."

If The Donald truly cares about the investigation of the causes of autism, this is the kind of enterprise that deserves his support - one that is based on science, where the heavy hitters of psychiatry, neurology, population biology, and genetics are teaming up to tackle this complex medical issue.

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Thanks for the excellent post. There is clear evidence supporting a heritable component in autism. As you note, studies to date suggest that the underlying genetics are likely quite complex. Recently, evidence has emerged supporting the concept that microscopic and sub-microscopic chromosomal rearrangements may be behind autism and some autism-like phenotypes in some cases. This observation should increasingly help with identification of the underlying genes in the future.

-Matt Mealiffe, M.D.

Although mercury can't seemed to be linked to autism, I would venture to guess that it isn't that great to be injecting into anyone. Granted, a little bit of toxins are actually good for the body because it does illicit a response.

I think the main reason that people tend to blame the shots has to do with the fact that the symptoms of autism usually don't present themselves until about the same time when they start receiving their vaccinations. Parents notice that their baby isn't developing normally and think (what happened to cause this?) and since you can't see genes, they assume outside influence. I can't help but wonder, however, if autism is a combination of factors. Perhaps there is a genetic condition which leads the individual to be susceptible to certain toxins or components in these vaccines.

I read an interesting article a while back that suggested that autism was caused by inflammation of various tissues (including the brain). I didn't know this until then, but autism is also characterized by many abdominal and digestive disturbances as well as the neurological effects. Seems most researchers are focusing on the brain when it might not just be the brain that's involved. Granted, I haven't heard much about it since... so it might have just washed over.

Um, viewing video tapes of children diagnosed with autism of when said children were babies had very telltale signs of autism. It's hard to diagnose out of the blue at that age, but if you review tapes it'll smack you upside the face.

I believe the suggestion of the abdominal and digestive disturbances was compete and utter poppycock. I'm fairly certain you are referring to the supposed link between the MMR vaccine-induced gut disorder "discovered" by Andrew Wakefield who applied for a patent on an MMR vaccine substitute and treatments for this MMR vaccine-induced gut disorder, on top of getting paid to by a group of lawyers to cast doubt on the MMR vaccine as a link to autism. Further the measles strain found in the Wakefield result was tracked through DNA tests to a strain not used in in the vaccine but one which Wakefield's lab was contaminated with. The co-authors withdrew and the Lancet retracted the paper and Wakefield is currently on trial for his behavior. This is where all this BS came from. Supposedly the MMR vaccine contains live virus which caused leaky-gut which allows toxins and chemicals to enter the bloodstream and damage the developing brain. -- It would be more amusing if it weren't believed.

Sure, mercury isn't great however we stopped using it in our vaccines in the US (some is used to preserve the out of country stocks which need to last longer) years ago. We stopped using mercury and the autism rates continued to be diagnosed at a greater rate. The actual rate of autism has remained constant, we just stopped calling every mental disorder "retarded". These rates of actual autism are independent of the vaccines in the country.

The FDA dropped the staggeringly tiny amount of mercury on the grounds that mercury probably isn't needed. Eating tuna is probably worse.

Autism is probably a heavily gene based disorder.

My Dad, one brother and I probably are on the Aspie end of the spectrum, but high-functioning kids weren't diagnosed as autistic under DSM III criteria. One daughter is an Aspie, one has PDD-NOS. Suggests at least some genetics to me. I do know I had an easier time coping as a child, as life was slower and less complicated. I still have a hard time dealing with a multi-tasking world, doubly hard for kids.

Until we understand the timing of various neuro-developmental processes in normal brain growth, and how these are different in the autistic brain, we won't know the causes of autism. If it were just toxins, we would have figured it out by now-like valproic acid.

Yet another academic with his head firmly up his ass...

Dude, did it ever occur to you that there could be genetic susceptibilities to environmental toxins like mercury? And that the increased amounts of mercury given willy-nilly in the vaccines just might have triggered neurological damage in those individuals?

I guess it impresses you that the IOM says no connection. You must not know any of the members - the National Academy of Sciences, it ain't.

My son is autistic and tested positive for mercury poisoning. I have a partial genotype for him - and he has point mutations in genes known to be involved in heavy metal metabolism.

I think you might be the misinformed one.

I'm with you John. My son is also autistic and has high levels of mercury in his system. To Abel Pharmboy: Jenny McCarthy isn't saying that Mercury/Vaccines are causing autism, she is saying that some children are unable to filter out the toxins from vaccines. Jenny specifically said that she IS NOT anti vaccine, she is ANTI TOXINS. You might want to consider attending a Defeat Autism Conference and hear DOCTORS who are PARENTS of autistic children who are making better, if not recovering, children from Autism by finding the cause of the autistic symptoms and treating them. And yes, one thing they are finding is that our kids have VERY high levels of mercury. I find it amazing how many people out there who DON'T have children with Autism are trying to beat down anyone who says they have found a cause. Read Changing the Course of Autism by Bryan Jepson.

Yes, of course there could be genetic susceptibilities. Of course, it is highly unlikely that a "genetic susceptibility" could cause a syndrome that is so clearly different from mercury poisoning in normal individuals, but it is possible. That is why there have been a number of studies of the supposed link, none of which have substantiated it. And elimination of mercury from vaccines has produced no decrease in autism incidence.

Beware of anybody who makes generalizations about "toxins." It is an absolutely certain indicator of somebody who doesn't know what he is talking about, or who is intentionally trying to deceive you. There are absolutely no useful scientific statements that can be made about toxins in general, because almost every substance is a toxin at some dosage level, and mechanisms of toxicity are so diverse.

Yet another academic with his head firmly up his ass...

John, as a fellow scientist, I am surprised that you would resort to an ad hominem attack to open your argument. But I'll let that pass and respond to you in a respectful manner instead.

Of course I realize that genetic variations can result in altered susceptibility to environmental toxins (as well as any xenobiotic). You and your son have my sympathy but I do not see evidence of causality, even if you have evidence of point mutations in heavy metal detoxifying proteins/enzymes (are you referring to something like metallothionein-III?). What is the evidence that your position is not simply a post hoc fallacy?

Indeed, not every member of the IOM Immunization Safety Review Committee was a NAS member but, as you know, the IOM is an arm of the National Academies. For example, I'd be the last one to question the credibility or expertise of people like Marie McCormick.

My concern is that even very intelligent people have been misled by the now-discredited mercury hypothesis when, in fact, substantial scientific evidence has accumulated to suggest there are genetic and cellular mechanisms underlying autistic spectrum disorders. The hysteria surrounding thimerosal and vaccines distracts from the real research questions and undermines the support for those investigators discussed in the Harvard Magazine article.

Heather, as trlll points out, what exactly are these toxins? What is their chemical identity? It seems that since the mercury militia has had the wind taken from their sails by scientific evidence, they have to find something else wrong with vaccines.

Thanks for blogging on this, Abel.

The idea of genetic sensitivity to mercury is not a new one. It's long been the anti-vaccine contingent's answer to the obvious reality that autism has a strong genetic component. Consequently, many sympathetic researchers have been looking for how this might happen. No results have emerged. If there were really a gene for mercury intolerance, I think it would have been found by now.

Moreover, if autism were caused by genetic mercury intolerance, autism would be more common among people who have been exposed to thimerosal-containing vaccines. It is not, and the studies that examined this question were more than powerful enough to find a difference in prevalence if one existed.

As it happens, a court decision issued very recently addressed the issue of "mercury genes." Its findings:

"More specifically, there is no evidence that the A1298C polymorphism in the MTHFR gene is associated with autism. A 2004 study by Boris, et al., and a follow-up study by one of the co-authors of that 2004 study, Jill James (among others), both showed no statistically significant association between the MTHFR 1298A/C polymorphism and autism.

"Further, the MTHFR 1298A/C polymorphism is common, occurring on average, across different populations, in about 34 percent of the population. In addition, the rate of occurrence of the MTHFR 1298A/C polymorphism varies significantly among different ethnic groups. It is well established that common genetic polymorphisms that vary across ethnic groups, such as the MTHFR 1298A/C polymorphism, are not considered by geneticists to be candidates for causation of a disease, such as autism, that has equal prevalence across ethnic groups.

"Lastly, the plaintiffs posit that the GSTMI null polymorphism is associated with autism. The GSTMI null polymorphism refers to a condition in which the GSTMI gene is missing. The purported association between the GSTMI polymorphism and autism has been investigated and rejected in several studies. No study has found an association between the GSTMI null polymorphism and autism. Further, there is no evidence that the absence of the GSTMI gene is associated with autism."

(Part of an excellent opinion reproduced at

Now, the courtroom is hardly the best place to get one's science, but this opinion does reflect the scientific consensus as far as I am aware.

And, John, the lab that told you your son "tested positive for mercury poisoning" - was this one of the consumer-oriented firms that compares provoked samples to unprovoked controls, when there is no meaningful reference scale for either?

Um. If there were any link to autism even a genetic one with mercury it would have been found. There's no correlation with mercury and autism. Our vaccines are now mercury free and have been and the rates of autism are completely unaffected. Just as the rates of mercury exposure aren't linked to autism rates. At a certain point here you need to invoke Himen's law: If there's nothing suggesting there's any there there, WHY ARE YOU ASKING FOR MECHANISMS!?

Seriously, the Bermuda triangle has no statically more likely number of vanishings or spooky things, than any equally large chunk of ocean. So there's no reason to ask why it does "something" for which there is no evidence whatsoever to suppose that it does.

Autism and Schizophrenia are known to be caused by maternal exposure to the flu virus.

Now that they know viruses can be involved they'll look for others.

This might be old news to some of you but pure genetic funding for autism is imploding rapidly. Looks like the theory of natural selection was right again.…

By Germophobe (not verified) on 05 Jan 2008 #permalink

Some very new research underway indicates that people with autism may not excrete mercury as quickly as "normal" folks. This might be due to an malfunctioning or missing liver enzyme; however, the significance of this is anyone's guess. I can't divulge my source because the research is just beginning. Keep your eyes open for reports on this in coming years. We also need to keep in mind that there is a host of other chemical factors that may or may not impact the frequence of autism, (e.g., analyses of placentas show at least couple of hundred environmental chemicals).

By Jim Seybert (not verified) on 07 Jan 2008 #permalink

Jim Seybert. Please read carefully.

Whatever your secret study shows, it will not change the fact that children exposed to thimerosal are not more likely to be autistic.

It doesn't matter whether their livers contain normal enzymes, abnormal enzymes, or a quart of Pennzoil. Unless there is more autism in the exposed than in the unexposed, there is no connection between thimerosal and autism.

The eighty-kajillionth study came out today affirming just this. Thimerosal exposure was cut back dramatically in the early 1990s (not that it was ever particularly meaningful, but it got significantly closer to zero). What happened to autism caseloads in the California developmental disabilities service system? Kept going up, and up, and up.

Hey look, it's the top health story on MSNBC:

Look folks you can debate forever but the mystery of Autism (and many other mental illnesses) has already started to fade away.

Autism is caused by an overactive maternal immune response, more specifically Interleukin 6. Flu virus triggers it, many other germs and viruses probably do as well. This is the direction the science is heading. It's GERMS and Viruses folks! It can also be the bodies response to these germs and viruses.

The sooner you accept it, the sooner you can move into the 21st century.

By Germophobe (not verified) on 07 Jan 2008 #permalink

The number of Autistic children will continue to rise. Don't be surprised if it hits 2% of all children in the coming decades.

Autism, like Shizophrenia is 2 or 3 times more common in cities than the country. Guess why? Pathogens. Cities are dirty.

No doubt genes play a part in susceptability. Pollution and stress may also play a small part in magnifying the damage.

Ironically vaccines will eventually STOP the spread of Autism even though a lot of people believe they cause it.

By Germophobe (not verified) on 08 Jan 2008 #permalink

Germophobe, I'd say that the Caltech paper on IL-6-mediated maternal immune activation is intriguing and speaks to a potential prenatal environmental influence, but remember that this study was only in mice. Moreover, the behavioral deficits in these mice are a model for schizophrenia and autism, but it is unclear how these outcomes extrapolate to the disease/disorder as they occur in humans. The fact that the offspring of IL-6 knockout mice do not respond similarly is again quite provocative but I'd caution restraint in overinterpreting the data. However, the fact that maternal exposure to environmental conditions that resemble influenza infection giving rise to offspring with compromised behavioral traits does indeed suggest that more attention should be paid to exposures to the mothers.


You are correct that more work is needed but this study doesn't exist in a vacuum.

OCD/Tourettes is now largely believed to be the result of bacterial infection, or the bodies response to it.…
"80 to 90 percent of those with OCD and Tourette's are strep carriers. "They may not get a sore throat but they can shed the bacterium," he explains. "Something is different about their immune system."…
How Strep Triggers Obsessive Compulsive Disorder � New Clues
Evidence is mounting that Narcolepsy is triggered by a Virus

By Germophobe (not verified) on 09 Jan 2008 #permalink

Hi Abel, I thought I should add just one more thing about heredity and Autism.

Genes that "cause" Autism have been found countless times. Here is one from today.…

Sadly these stories share a general theme.

The headline says "Gene for Autism Found!"
The fine print explains that the gene only raises the risk factor. How or why the risk goes up is never explained because they don't know.

The reality is that natural selection works, thanks Darwin. It almost always takes some hefty environmental input to trigger common types of illnesses in children. If it happens to more than 1 in 1000 kids you can bet that negative environmental input plays a decisive role. In fact in most cases heritable genetic disorders don't occur in more than about 1 in 10,000 kids.

If you google genetic disorder you will see what I mean. 8-)

The only known exceptions fall into the category of Heterozygote Advantage. These are exceedingly rare, group specific and fairly obvious.

By Germophobe (not verified) on 09 Jan 2008 #permalink

Sorry, one last thing.

I don't mean to exclude the possibility that genes can be damaged by the environment and then passed on to offspring. Genetic disease due to pathogens, pollution, radiation etc. could certainly be a part of the equation.

In the case of disorders that have been around before preindustrial societies, pathogens are the most likely culprit.

By Germophobe (not verified) on 10 Jan 2008 #permalink