The last issue of the prestigious Journal of Child Psychology and Psychiatry included a study that examined the role of parental age on the risk for autism among two very large nationally representative cohorts in two separate countries (Sweden and the UK). The basic question – whether the parents’ age impact the risk of having a child with autism – is not that exciting or innovative as several studies have shown that older parents, especially dads, are more likely to have children with autism. What was really interesting about this study is that it was conducted with an incredibly large numbers of twins, which can help us understand the association between parental age and the relative environmental vs. genetic contributions to autism.

Before I talk about the study I want to provide some background on autism research and twin studies. The question that most behavioral geneticists ask is NOT whether autism is genetic or environmental. There is enough data to show that autism is NOT purely genetic and that autism is NOT purely environmental. The consensus is that autism is a very heterogenous condition that is likely due to multiple genetic and environmental factors.  So real question is what are the relative contributions of the environment, our genes, and other bio-social processes to the development of autism. To this end, behavioral geneticists examine the similarity between monozygotic (MZ) vs. dizygotic (DZ) twins to determine the relative genetic vs. environmental contributions of a specific condition. Specifically, if the correlation within MZ twins in regards to the rate of a disorder is greater than the correlation within DZ twins, then you would assume a significant genetic contribution. Why? MZ twins are genetically identical while DZ are not.  If a disorder has a large genetic contribution, then you would expect those twins that are identical to be more likely to both have the disorder than twins that are not identical. In contrast, in a disorder with little genetic contribution, DZ and MZ twins would be equally likely to share the disorder since the difference in how genetically identical they are would make little difference.

So in this study, the authors examined data from two large twin cohorts from Sweden (N=11,122) and the UK (N= 13,524) who were assessed at age 9 with two different autism scales/interviews. In Sweden the children were assessed with the Autism-Tics, AD/HD, and other Co-morbidities (A-TAC). In the UK, the children were assessed with the Childhood Autism Spectrum Test.

The results:

The graphic below shows the percentage changes in the probability of having a diagnosed ASD by having a father in different age groups.

Autism and Fathers Age

As you can see, compared to 24-34 year old dads, there was a large increase in the odds of having a child with ASD (almost 100%) for younger dads, a similar increase for dads 35-44, and a very large increase (over 200%) for dads older than 51. However, only the change in fathers >51 in Sweden was statistically significant. The other changes only approached significance, likely because of the low rates of ASD among these cohorts.

As comparison, below you can see the changes in ASD traits for children of fathers in different age groups.

Autism traits and father's age

This time, the increase in autism traits for children of young fathers (<25) and older (>50) fathers is statistically significantly when compared to kids whose fathers were 25-34. So this study is consistent with previous research showing an increased risk of ASD among older fathers. However, the study also shows an potential increased risk of ASD for younger fathers as well. There was no effect of maternal age on the risk of ASD.

What about the role of parental age in the relative genetic/environmental contribution to ASD diagnoses?

Below is a graph that presents the correlation within MZ or DZ twins for different paternal age groups.

MZ and DZ twins and autism

You will notice that the correlation between the MZ twins is always higher than the correlation between the DZ twins, suggesting some genetic contribution to the disorder. That is, MZ are more likely to BOTH have ASD than DZ twins. However, notice how the difference between the DZ and MZ twins is reduced for the older parents, in both Sweden and the UK. What does this mean? It means that the relative genetic contributions to ASD appear to decrease for older fathers. Now see below the raw correlations for all age groups:

Autism in MZ and DZ twins by fathers of different age groups

What it is interesting about these data is that the correlation within the MZ increases with the fathers age. For example,  MZ twins of fathers over 40 have an almost 1-to-1 correspondence of the disorder. That is, if one twin had the condition, the other twin almost always had it too. Does this means genetic? Well, at the surface you would think this means genetic, after all both twins are genetically identical and both twins have the disorder. However, remember that MZ were conceived from the same sperm, and in this case, from the same sperm that may be ‘damaged’. So the increase concordance among MZ twins for older dads is not necessarily reflective of a genetic anomaly. In fact, the authors indicated how this effect may be due to the prolonged exposure to environmental toxins among the older fathers leading to sperm mutations. If that hypothesis is correct, it could be the environment, and not the genes, what is responsible for the increase risk in ASD among children of older dads.

The reference:
Lundström, S., Haworth, C., Carlström, E., Gillberg, C., Mill, J., Råstam, M., Hultman, C., Ronald, A., Anckarsäter, H., Plomin, R., Lichtenstein, P., & Reichenberg, A. (2010). Trajectories leading to autism spectrum disorders are affected by paternal age: findings from two nationally representative twin studies Journal of Child Psychology and Psychiatry DOI: 10.1111/j.1469-7610.2010.02223.x

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12 Responses to Autism: Environmental and Genetic? Clues from parental age.

  1. JulieL says:

    “In fact, the authors indicated how this effect may be due to the prolonged exposure to environmental toxins among the older fathers leading to sperm mutations” So do I have this right: old sperm becomes damaged by environmental toxins purely by being arounded by environmental toxins for longer duration = possible cause for autism. But what about the younger men and their increase? Perhaps I missed where you mentioned how this hypothesis includes the younger men, but I feel like I’m missing something here.

    • @JulieL, thanks for bringing this up. The authors touched on this issue by stating that the risk associated with younger age is probably different in origin than the risk associated with older age.

      @MJ, excellent point. However, the fact that they have greater risk than other siblings does not refute the potential genetic role, but it highlights the strong role of shared environmental factors (including in utero exposures).

      @DSC. You are correct, this has been a common interpretation of the role of genes in the differences in concordance between MA and DZ twins. Under this hypothesis, there is still a genetic role: providing a shared vulnerability to environmental exposures.

      Now, I honestly think that the ‘autism must be genetic” theory is mostly pushed by the media and not the actual behavioral geneticists. Most of these scientists are not fundamentalist – that is, they understand and accept the evidence that genetic input in the development of these disorders is limited. I am yet to read a single paper where a scientist declared that autism was totally, or mostly, genetic. Yet, I do agree that spending more money on examining the role of environmental factors in the development of autism is necessary.

  2. MJ says:

    One of the other results that I always find interesting but never seems to be highlighted is that DZ twins seem to be more likely than other siblings to be concordant for autism. If autism is predominately genetic, shouldn’t DZ twins have the same chance of both having autism as would any other siblings?

  3. DSC says:

    Since MZ twins share the same genetic traits, then in vitro they have the same response to caffeine, aspartame, lead, mercury, and other possible environmental causes of autism. However, DZ twins do not have the same genetic response to environmental factors but still show a high concordance, and thus response, to environmental factors.

    We may be simply ignoring two important facts that mislead the crowd believing autism has a primary or largely causative genetic factor:
    - children in the same family have parents who basically do the same things prior to and during pregnancy. No study has shown that parents of autistic children fundamentally change their eating and other bio-habits after a diagnosis. They tend to eat and drink and smoke with little variation, certainly not enough to rule out in vitro environmental causes for twins, not genetic
    - it is well known that during development biological effects can change genetic outcomes. Again it could simply be that MZ twins and DZ twins, being in the same womb, face the same hazards and thus similar effects to DNA expression due to environmental factors

    As one doctor told me, it could be the ‘baseball bat’ approach that we’re missing. His point was that no matter what your genetics or health, getting hit in the legs hard enough with a bat would break them, regardless of genetic factors.

    Are we spending too much money chasing ghosts with genetics? Are we missing the baseball bat hitting us all, but thinking that only those with certain ‘genetic traits’ get broken legs, when really only some get hit hard?

    Could the simple fact that leaded gas has been used for 80+ years be the smoking gun? AC/DC electrification? Industrial plastics? Generations of inoculations and vaccinations, not ‘a’ vaccination? Processed cheese slices?? What class of ‘toxins’ is to blame?

    I tend to believe that we are simply overlooking the obvious in defining autism and its causes, and I’m missing it too. This isn’t Down’s Syndrome or CF, after all.

    Even I don’t believe the current definition is accurate or restrictive enough, but the fact that truly autistic kids are growing in number is fact enough that genes are a much less important factor than environment. What are we overlooking??

  4. MBM says:

    What we might be overlooking is that everyone labeled Autistic may not be autistic. The significant increase in diagnosis reminds me of the repressed memory era, or any other high profile anomaly that everybody suddenly has before it dies out or another new thing comes along.

  5. JulieL says:

    Nestor – Did the younger men have different environmental toxin factors, than the older men (although I’m unsure how they could define what the environmental factors would be)? Or did they assume another reason outside of environmental toxins were the reason behind the increase in younger men?

  6. Neuroskeptic says:

    Thanks for this very clear explanation of these findings. The young-father effect surprised me: it seems consistent since it was seen in Sweden and the UK. Do the authors try to explain it?

  7. Jen says:

    Fascinating, and thank you for the great explanation. It’s very interesting to me as I have DZ triplets who were all diagnosed on the spectrum, and I’m always fascinated by genetics studies.

    Again, thanks for the clear explanation- it helps to have an informed guide.

  8. Doron says:

    form:
    http://www.pnas.org/content/94/16/8380.abstract?ijkey=b074bd3ac8068d01106791755a16a7b939f695af&keytype2=tf_ipsecsha

    “The human mutation rate for base substitutions is much higher in males than in females and increases with paternal age….”

    Base substitutions (SNP) may lead to abnormal biochemistry in the children and make them more susceptible to the same environmental stressors that hit the parent.

  9. RAJ says:

    “Since MZ twins share the same genetic traits, then in vitro they have the same response to caffeine, aspartame, lead, mercury, and other possible environmental causes of autism. However, DZ twins do not have the same genetic response to environmental factors but still show a high concordance, and thus response, to environmental factors”.

    Autism twin studies to date are all based on classical twin study design which presumes an equal prenatal environment assumption. That may be a poor design study method since only two thirds of MZ twins are monochorioic (same placenta) while one third of MZ twins are dichorionic (different placenta) as are all DZ twin pairs, and therefore do not share exactly the same prenatal enviroment.

    No twin study in autism has ever segregated concordance rates of MZ twins by placentation status.

    The California Autism Twin Study (CATS) has closed its recruiting phase with 225 pairs of twins included in the study. This is the first population based study to record chorion type (where the information is available).

    If autism is genetically predetermined concordance rates in MZ twins segregated by chorion type should be the same. If autism is a strongly environmental disorder concordance rates in MZ twins who have developed prenatally in seperate placentas might be the same as concordance rates in DZ twin pairs.

    This study, if they have managed to recruit a large sample of MZ twins with unambigous chorion data, will be the most important twin study ever published.

  10. RAJ says:

    “One of the other results that I always find interesting but never seems to be highlighted is that DZ twins seem to be more likely than other siblings to be concordant for autism. If autism is predominately genetic, shouldn’t DZ twins have the same chance of both having autism as would any other siblings”?

    The twin study pubished by the Interactive Autism Network (IAN) found 31% of DZ twins were both diagnosed with an ASD. Sibling recurrance rates are between 3-5%.

    The risk for ASD in both DZ twins may be up to 10 fold higher compared to sibling recurrence rates which suggest that environmental actors have been vastly understated.

    http://www.ncbi.nlm.nih.gov/pubmed/19805709

  11. Valerie says:

    The majority of research studies concerning autism mention the strong

    basis of genetic factors for autism’s onset. However, as many other

    disorders in psychology, environmental factors play a significant role,

    too.

    Thus, I guess we have not focus only on genetic or environmental

    factors.

    Conversely, we have to examine these both factors in order to have

    much

    more complete picture of what is that creates autism.

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