Friday, April 07, 2006

Twin Concordance Not 100%

According to a common argument, autism is a pathology resulting from an environmental trigger (a virus, poison or injury) because its identical twin concordance is not 100%. I do not believe it is reasonable to expect concordance of any subjectively evaluated behavior to be 100%, and I will try to support this claim by comparing various behavioral and physical phenotypes.

(There's also an argument to be made about phenocopies caused by environmental triggers, but I won't discuss that in this particular post).

Autism

The first identical twin study on autism was Folstein & Rutter (1977). It found a concordance of 36% in identical twins. This seems low, but note that they found a concordance of 82% for "cognitive abnormalities". This is a key to how conceptions of autism have changed since that time. Folstein & Rutter probably used a very narrow definition of autism. Other studies since have indicated that narrower definitions give lower concordance, which is not surprising.

Folstein & Rutter (1977) also found a 0% concordance for fraternal twins. This needs to be taken with a grain of salt, because they only had 10 fraternal twin pairs. In other words, this only says it's lower than 10%, with a significant margin of error.

The highest concordance to date was found by Ritvo et al (1985). It was 95.7% for identical twins, and 23.5% for fraternal. They probably used a broad definition of autism in this case. A positive aspect of this study is that they had 23 identical twin pairs, many more than usual.

The twin study considered to be the best one methodologically speaking is Bailey et al (1995). It found a 60% concordance of autism in identical twins and 0% in fraternal. It also found a 92% concordance for a broader autism spectrum in identical twins and 10% in fraternal.

It might be of interest to compare fraternal twin concordance with sibling concordance to try to determine environmental influence. But again, small sample sizes make this impossible within a comfortable margin of error. Sibling concordance is anywhere between 2%-4% for classic autism and 10%-20% for a broader spectrum, which is not inconsistent with fraternal twin data.

Homosexuality

Kallman (1952) was the first twin study on homosexuality. It found a 100% concordance in identical twins, and 42.23% in fraternal.

This study has been contradicted by more recent ones.

Heston & Shields (1968) found a concordance of 20% in identical twins. The study sample of 5 pairs limits its conclusions, however.

Bailey & Pillard (1991) found a concordance of 52% in 56 pairs of identical twins, and a concordance of 22% in fraternal twins.

Left-handedness

A commonly cited number for concordance of left-handedness is 12% in identical twins, compared to a background of 8%. If this is correct (not much literature on the subject) then left-handedness is not very heritable.

Intelligence

The number usually cited for concordance of intelligence in identical twins is 80%. This, of course, must depend on the IQ range used to determine concordance. Aggregating various studies, there's about 87% concordance in identical twins reared together, 76% in identical twins reared apart, and 56% in fraternal twins reared together [ref]. Heritability estimates seem to range between 0.4 and 0.8.

Personality

Across many personality traits the average concordance in identical twins is 50% and 30% in fraternal, per Bouchard & McGue (1990) and Loehlin & Nichols (1976). Heritability estimates range from 0.40 to 0.50.

Eye Color

Let's now look at a physical characteristic that can be evaluated fairly objectively. Bito et al (1997) found a concordance of 98% for eye color in identical twins and 49% in fraternal. These results are not surprising.

Concluding Remarks

Autism concordance in identical twins is not 100%, which suggests there is likely some kind of environmental influence in autism etiology. The assumption that this influence must be in the form of an environmental insult (a poison, virus or injury) is simply a reflection of expectation bias in the part of researchers and parents. Autism is extremely heritable even when compared to personality and intelligence. It is not far-fetched to suppose that the kind of subtle environmental influence that results in discordant personality and intelligence in identical twins also plays a role in autism.

11 comments:

  1. Identical twins never have the same fingerprints. This is why identical twins don't have the same brains. There is a natural radomness built into genes that people in general don't understand. Even if chemical exposure, food, temperature, noise, germ exposure, whatever ... were controlled absolutely exactly for two identical twins from the time the egg split until 2 years of age... they would still have different brains.

    If you think about taking a handful of 100 numbered metal BBs and an identical handful of 100 numbered BB's and two identical trays about 2 feet across with a rim to keep the BBs from rolling off.

    then you drop the BB's from both hands onto the separate trays, even if the BB's were placed both in your hands in an identical way, the places that the BBs would end up on the two trays when they stopped bouncing around and rolling, would be different.

    That's the kind of randomness that you find in the way that genes interact with each other. The genes are making stuff like bone proteins and hormones and blood... all this stuff interacts with itself within the child. In the real world, the mom is moving, gravity is pulling differently on the two twins, they are hearing slightly different sounds, they are feeling slightly different things, the one doing the kicking doesn't feel the same thing as the one being kicked inside the womb... each bump and sound potentially wires up a new neuron.

    There may be very subtle differences in nutrients, and conceivably one twin could get a dose of viruses that the other wouldn't, but that seems really unlikely to me... same for drugs, seems like both twins would get nearly the same exposure to drugs or alcohol the mom would take in...

    The difference between two identical twins is mainly going to be about epigenetics, in the sense of my BB illustration. It's uncontrollable, and why a cloned tabby cat will not look like the one it was cloned from... the spots are random, like fingerprints.

    A cloned Dalmatian dog wouldn't look like the original.

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  2. That's a good way to explain it Camille. There could be nearly infinite subtle random environmental factors that affect outcome, which are impossible to control. This results in a spectrum with infinite levels of "severity" and could land two twins on either side of a diagnostic threshold.

    I think it's important to note that such factors affect all humans, not just those classified as disordered.

    Subtle differences in the womb probably have more of an impact than anything that happens outside the womb, but I'm just guessing.

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  3. When I gave birth to my twins at 44, and realized one was autistic, I at first was SURE that I had poisoned my baby with the old dental amalgams still in my molars from nearly 40 years ago. Either that, or the numerous medications I had to take while pregnant because of diabetes, preterm labor, etc. Finally, the obvious hit me...his twin was neurotypical. If I had "poisoned" him, I had poisoned the twin as well. Yes, there are gender differences, and yes, there are genetic differences. I simply don't believe that my uterine environment could produce one healthy and one poisoned child simultaneously. That was the beginning of the end of my lending any credence whatsoever to the mercury hype.

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  4. Changes that happen earlier have bigger impacts that changes that happen later. There's a term called generative entrenchment that is related to this idea. It's bascially that early fetal development in vertebrates (for instance) can only look a certain way. to go from a blastocyst to a thing with a spine, there are certain logical step that have to happen, so that an embryo for a bird and a monkey a dog and a human look alot alike in the very beginning...

    But also the embryo is when you don't want something serious going wrong because of the downstream effects. I sort of mentioned it in the 'when we were small, very small' blog. The face is being built before there is anything like a face there to see. If there's damage of some kind or a change of some kind in the proto proto proto face, it will be there in the final face. Same with the brain.

    There's plasticity that helps to accomodate damage later on, but some kinds of damage early on is too serious. Like if the baby's face doesn't close, he can have a big gap in the upper palate, that never fills in on its own. Thank goodness for surgeries for cleft palate.

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  5. What do you make of the difference in concordance of intelligence of twins reared together vs. those reared apart? Looks like genetics trumps environment outside the womb, but there's something to be said for the shared environment (family/school/community).

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  6. As they age, twins' genetic makeup differs more and more. Saw a study (will have to dig for it) where they compared DNA from twins of all ages. The environment continous to alter gene expression throughout life, so older twins accumulate differences. One twin may get Alzheimers 10 years earlier than their twin.

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  7. Identical (MZ) twins born to HIV positive mothers have a higher concordance rate than fraternal (DZ) twins. The report from the International Registry of HIV exposed twins (1996)reports that of the twin pairs in that registry 17 of 19 MZ twins were both HIV infected and only 26 of 43 DZ twins were both HIV infected.

    Higher concordance rates in MZ twins compared to DZ twins are commonly found in many medical conditions that would not be thought of as genetic 'condition'.... including HIV, cerebral Palsy, Fetal Alcohol Syndrome to name a few.

    Concordance does not prove nor disprove genetic causation since MZ twins poossess an identically strong (or mild) genetic laibility to the same gestational insult.

    Schizophrenia research reported that the concordance rate for schizophrenia may have to do with the prenatal environment. The concordance rate for MZ twins is much greater in MZ twins who developed in a single placenta compared to MZ twins who developed in seperate placentas and did not share the same prenatal environment.

    Simple conclusions drawn from raw concordance rates among twin pairs about gentic causation deserves the Scottish verdict of 'Not Proven'

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  8. This is issue is to what degree is mother's testosterone levels influenced by environmental factors.

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  9. Susan -- may I quote your twin-story to folks who stekk stories aout mercury?

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  10. Susan -- may I quote your twin-story to folks who tell stories about mercury?

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