Wednesday, October 7, 2009

Autism in Twins

One of the more common things that you will hear about autism is that it is a genetic condition or that it has a "strong genetic component". I think that most people hear this and assume this means that there is some gene or mutation that runs in families that "causes" autism.

Unfortunately, autism is not so simple.

Researchers have spent a lot of time and effort searching for genetic causes for autism, and with the exception of Rett's Syndrome, have come up empty handed. Sure, there have been some small successes here and there but most of the promising leads don't pan out. A study will find a small group with a possible genetic commonality only to have the next study will come along and fail to reproduce the finding.

This leads to the question of why do we think that autism is genetic? If numerous large studies have failed to find anything that people with autism have in common at the genetic level, why exactly do we think that autism is genetic?

The answer is twin studies. There have been several studies done in the past that show that identical twins almost always both have autism while fraternal twins don't. This is taken to mean that autism must be genetic because, if identical twins both have autism and fraternal don't, it must be the shared genetics that makes the difference.

With that in mind I would like to point out the most recent study of autism in twins that was just published in Archives of Pediatrics & Adolescent Medicine -


In this study, researchers from the Kennedy Krieger Institute and Johns Hopkins looked at 227 twin pairs from The Interactive Autism Network (IAN) where at least one of the twins had a form of autism. IAN is an Internet based resource where parents can contribute information about their children with autism which can then be used by researchers. As a result of utilizing IAN, the researchers were able to look at more twins than any study has done before (previous studies had less than 50 sets of twins).

A total of 227 sets of twins took part in this study - 67 pairs of identical twins (58 male, 9 female) and 210 pairs of fraternal twins (97 male-male, 23 female-female, 90 female-male). For those of you who are not familiar with twins, the simple rule here is that fraternal twins are basically the same as siblings that happen to be born at the same time while identical twins share the same genes.

The results show that identical twins were about 88% likely to both have autism as well as (~ 90%) to have the same form and severity. However, what was not expected was that in all in male identical twins this rate was 86% while in female twins the rate was 100% and none had aspergers. Unfortunately, there were not enough female identicals for this finding to reach statistical significance but it was still interesting nonetheless.

Prior studies have shown that identical twins will both have autism somewhere between 60% and 95% percent of the time, so this finding was in line with prior results.

For fraternal twins the overall concordance was 31% which, while higher than was though in the past, is not too badly out of line. The interesting part here is that male-male fraternal twins had a 40% chance of both having autism, which is significantly higher than other types of fraternal twins.

Most other studies studies have placed the rate for fraternal twins to be the same as non-twin siblings, although a recent study out of Japan also showed a higher rate for fraternal twins.

For reference, in non-twin siblings, the rate is thought to be somewhere from 5% up to as high as 20%.

So what does this all mean for autism being genetic?

Well, because the majority of identical twins will both have the same type and severity of autism there clearly is something going on at the genetic level that can cause or predispose someone to autism. But, in at least 10% of cases, identical twins do not share their autism and in another 10% beyond that the severity level can differ.

This tells me that while genetics does play a strong role, it is not the entire story. There is something other than genetics that can determine whether someone will develop autism.

If you look at fraternal twins, they are more likely to both have autism than normal siblings. In the case of male-male fraternal twins that risk can be almost double. Remember, the only difference between fraternal twins and regular siblings is that they share the same prenatal environment and grow up in the same environment at the same time.

If autism was solely genetic there would not be a difference between normal siblings and fraternal twins, and yet there is. And in the case of male-male fraternal twins the risk is much higher than in normal siblings, and that shouldn't be the case either.

If you put these two parts together it becomes clear that there is likely something other than genetics that can cause autism. Or in other words, it is likely that there is a genetic predisposition that is triggered by some sort of environmental influence.

Obviously, I am simplifying things things a bit here and there could very well be other factors at work here. This is one study and, interesting though it is, it does not prove that there are environmental influences. But at the same time it does strongly point in that direction.

Maybe it is time to stop spending so much time looking for the autism's smoking gene and start spending more time looking at what environmental influences could be triggering it? Or here is crazy thought, how about if we devote some time to looking for the physical changes that autism causes in a person. Perhaps if we know what autism is and how it effects the body we might have a better shot at treating it?

Just food for thought.

8 comments:

  1. It is long past time to start studying potential environmental factors involved with autism. While the twins study may be more recent Baron-Cohen has made the same point publicly on at least 3 previous occasions. Binstock highlighted the fact in 1999 that autism research funding was directed almost exclusively toward genetic based studies a trend which continues today.

    If all that is studied is genetics, genetics will be the only thing found, the only explanation for autism.

    Let's study the environmental causes including proper vaccine studies.

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  2. Is there anything behavioral or neurological that has 100% concordance in general population identical twins? Anything at all? Something like personality, intelligence or even brain mass.

    Even something like height is probably not 100% concordant in MZ twins. Suppose I define concordance as "within half an inch." Which environmental poison explains any lack of concordance?

    I guess if you look at autism as a simple biological entity like "eye color" you might expect 100% concordance if it's genetic. But such a thing doesn't exist, any more than "short stature" exists as a biological entity.

    Incidentally, have the genes for height been discovered? Is there a way to predict someone's height accurately just by looking at their DNA? I suppose height is not heritable then.

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  3. "Is there anything behavioral or neurological that has 100% concordance in general population identical twins?"

    Yes, there are many things that are almost 100% concordant in identical twins, especially when they are very young.

    Most of the differences that can exist will develop over a lifetime of living different lives or in a different environment.

    "Something like personality, intelligence or even brain mass."

    I can tell you from experience that personality is certainly not genetic. There may be shared aspects of character, but identical twins certainly have their own personalities.

    Intelligence is strongly controlled by genetics, at least at a young age. At older ages intelligence does not depend so much on native ability as experience and learning.

    Brain mass I suspect is genetic (at least if you use a proxy of head size).

    "Even something like height is probably not 100% concordant in MZ twins."

    Actually, in young identical twins height and weight are almost always in lockstep. If there was a significant difference it would actually be a cause for concern.

    My girls have always been within a few ounces in weight and the same height for their entire lives. Other families that we know with identical twins have had the same experience.

    "Which environmental poison explains any lack of concordance?"

    Environmental influence does not equal poison.

    "I guess if you look at autism as a simple biological entity like "eye color" you might expect 100% concordance if it's genetic."

    This is actually my point. If autism were simply a matter of genetics then the concordance in identical twins would be almost 100%. Yet the range, which is somewhat consistent across different groups and studies, is somewhere between 60 and 90 percent. And even if both twins have autism, they are not always concordant in severity.

    The entire point here is that identical twins are identical (or close to it) on a genetic level (and when born an epigenetic level) - the only thing that differs between the two of them is their environment (possibly prenatal environment as well). If you see physical or neurological differences between identical twins it is almost certainly caused by their environment or lifestyle.

    When you then add in the male-male fraternal twins having a higher rate than ordinary siblings and I think it becomes clear that there is some environmental influence.

    "Incidentally, have the genes for height been discovered? Is there a way to predict someone's height accurately just by looking at their DNA? I suppose height is not heritable then."

    I have no idea of the heritability of height but I am sure that there is some genetic component to it. But, if I were going around and saying that height is genetic and then saw that only 90% of identical twins were of similar height, I would immediately conclude that there was some other factor involved. The same logic applies here.

    Just to be clear, I am not saying that autism is 100 percent environment either. I am simply saying that there is some factor involved in developing autism other than genetics.

    There has much a lot of research done to find the genetic smoking gun - most of which has come up empty.

    There has not been nearly as much work done looking into the environmental triggers of autism. If there is a trigger, and we can find it, then perhaps we can prevent autism from developing in the first place.

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  4. But, if I were going around and saying that height is genetic and then saw that only 90% of identical twins were of similar height, I would immediately conclude that there was some other factor involved.

    Why? It depends on how you define "similar height." If "similar height" is "within one foot" then concordance in MZ twins is probably going to be 100%, but then concordance will also be high in DZ twins.

    Would 100% concordance defined in this manner mean there is no environmental influence in height?

    If you make the definition very narrow, then concordance will be lower. If it's narrow enough, concordance can be 0%.

    It's the same with everything that may be characterized as a spectrum, and there's no need for complicated environmental explanations, unless you find that there's not a whole lot of difference between the concordance of MZ and DZ twins.

    MZ twins are not exactly identical, and this is fine. For example, what explains the fact that MZ twins have different fingerprints? This is not a big unsolved mystery. There's randomness in the world, and that's that.

    BTW, studies say that the MZ concordance of intelligence is 70% to 80%. I seriously doubt there's a discernable "environmental cause" for this.

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  5. "Why? It depends on how you define "similar height.""

    Of course it depends on your definition - but concordance for height would not be within a foot nor would it be within a millimeter. You need to pick some reasonable definition.

    But, if you looked the identicals who were 3 years old and one was two inches taller than the other you would have to conclude that something other than genetics caused the difference. If they were half an inch that would be close to the limits of precision and I would call that concordant.

    If you have fraternal twins there would be no expectation that they would be any closer in height that normal siblings.

    In the case of autism, and in the case of this particular study, the definition of concordance was fairly broad - so lack of concordance is meaningful. For example, one twin could have had autism and the other pdd-nos and they would have called them concordant.

    "It's the same with everything that may be characterized as a spectrum, and there's no need for complicated environmental explanations,"

    Identical twin do not do a spectrum - if is something is genetically controlled and the twins are young the only different is environmental.

    "unless you find that there's not a whole lot of difference between the concordance of MZ and DZ twins"

    Or if you find that fraternal twins have a higher rate that ordinary siblings. That implies an environmental influence.

    "MZ twins are not exactly identical"

    Yes, they are, except for changes caused by their environment. And this is especially true for very young children - the age were autism develops.

    "what explains the fact that MZ twins have different fingerprints"

    Fingerprints are not genetic.

    "There's randomness in the world, and that's that."

    Not in the genetics of identical twins - they are literally the same organism for the first week or two of their life. If there is a difference, especially a significant one like autism, there is something that "caused" the variance.

    "BTW, studies say that the MZ concordance of intelligence is 70% to 80%."

    At what age?

    " I seriously doubt there's a discernable "environmental cause" for this. "

    Of course there is. If one twin studies more or is more interested in learning then that twin will have a higher intelligence score.

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  6. But why would one twin be more interested in learning than the other, if they are identical? What causes that? You really didn't find an environmental cause - which was a speculative one either way.

    There's not a huge difference in the concordance if you compare twins reared together and those reared apart. It's reasonable to assume that innumerable little random things that happen in life probably account for most of the lack of 100% concordance.

    There's no question that there are factors that influence things like intelligence. But I'd suggest that you can never explain the entire discordance, nor will there ever be a means to precisely predict someone's IQ just based on their DNA and known risk factors.

    To use another example, what do you make of the fact that homosexuality is not 100% heritable, even though it does appear to be highly heritable?

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  7. Joseph,

    I think you are missing the larger picture when it comes to identical twins. They are two individuals who share the same genetic code but they are not the same person.

    There are a lot of things that they do have in common, even beyond the obvious physical characteristics. They are going to have a similar level of mental ability and they will even share some of the same personality traits.

    When they are born, depending on the exact configuration in the womb, they will have come from identical genetic material and have an almost identical prenatal environment. There will be very, very little, if any differences between the two on any trait that is strongly genetic.

    As the twins get older the environment will start to act on them in subtle, small ways and giving them small differences on an epigenetic level. Again, these are normally very. very small and act very, very slowly to the point where, after a lifetime of living, you will only find small differences.

    Identical twins also normally share the same physical environment when very young, some time up to and including sleeping the same room and possibly the same crib. (At least in my experience and what other parent's of twins have told me). If there is something in the environment there is an excellent chance that they will both be exposed to it.

    As the twins get older their personalities will (again normally) evolve into who they are becoming. Although almost from the start you can tell that the twins do have different personalities and are not the same.

    Personality is not environmental. It may be shaped by experiences, but identical twins most certainly come equipped with their own personality.

    Enter autism. Almost by definition, it has to start showing its ugly head by age 3. Most people will tell you now that there are earlier signs of it, almost back until birth. I believe you are one of the people who believes that.

    If autism were solely genetic then there would be almost no possibility that the twins would be disconcorant - it certainly would not be 10-40 percent. Not at this young of an age where most development is still driven by genetics and the twins are so close together.

    There have actually been one or two genetic studies down on identical twins who had vastly different seventies of autism that looked for genetic and/or epigenetic level differences between then twins. I think they found even still something like 99.6% concordance on the epigenetic level.

    But even a 0.4% difference in very young identicals would be puzzling and there would have had to be something that caused the difference. And random difference is not a cause - identical twins are not randomly different, they are only different were some process caused the difference.

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  8. Just saw this post and as a mom to identical twin boys, I found the post and the discussion in the comments fascinating.

    Both of my children have autism, but at completely different ends of the spectrum. I believe there is a genetic reason they have autism to begin with, but I absolutely believe there was an environmental trigger for my more severely affected son.

    I guess we'd fall in the 10% of the IAN survey (which we were a part of ), with different severities of autism.

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