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Sunday, September 21, 2014

Direct Evidence that a Father’s Age Affects Autism Risk

Posted by jlwile on October 10, 2012

A magnified image of stained human sperm (click for credit)

While there is some disagreement on the subject, most medical scientists would agree that Autism rates are on the rise in the U.S. and in many other parts of the world. What’s the reason for this increase? Like most medical issues, there are probably a variety of reasons. Some have suggested that the increase in autism can be linked to childhood vaccination, but the data argue strongly against it. Most likely, there are a series of genetic and environmental factors that play a role in the increase.


For quite some time now, there has been strong evidence that the age of the father has a significant effect on the chance of his child having autism.1 There has been evidence that the mother’s age also plays a role, but its effect is much smaller.2 However, these studies simply demonstrate a correlation between parental age and autism. They do not show that increased parental age plays a direct role in the cause of autism. However, a recent study published in the journal Nature has changed that. It seems to provide a direct link between the age of the father and autism in the child.

The authors of the study examined the entire genomes of 78 parent-offspring trios (mother, father, and child) to directly determine what mutations the child received from the father’s sperm cell and what mutations the child received from the mother’s egg cell. Because they were specifically interested in the cause of neurological disorders, they used a large number of trios that contained a child with either autism or schizophrenia. In the end, 44 of the children had autism spectrum disorder, and 21 were schizophrenic. In addition, the genomes of 1,859 other people were sequenced to serve as a population comparison.

The authors focused on the de novo mutations in the children. These are mutations that do not exist in either parent but do exist in the child. Thus, they must arise from a mutation that occurred when the father made his sperm or the mother made her egg. Such mutations happen in every production of egg and sperm cells, and the authors wanted to know which parent (if either) was more responsible for them. The results were surprising, to say the least!

When they looked at de novo mutations in the children’s genomes, they found that the vast majority of the child’s mutations could be accounted for by the father’s sperm.3 The mother’s egg passed on some mutations, but not nearly as many as the father’s sperm. In the end, they found that the father transmitted almost nine times as many de novo mutations as the mother. They further found that the number of mutations transmitted by the father’s sperm increases linearly with his age! As the authors state:

Seeing an association between father’s age and mutation rate is not surprising, but the large linear effect of more than two extra mutations per year, or the estimated exponential effect of paternal mutations doubling every 16.5 years, is striking.

So for every year a man waits to have a child, he will pass on two extra de novo mutations to his child. The authors go on to note that the average age of fathers has increased over time in the country where the study was done (Iceland). They then say:

Demographic change of this kind and magnitude is not unique to Iceland, and it raises the question of whether the reported increase in ASD diagnosis lately is at least partially due to an increase in the average age of fathers at conception.

In the end, then, I think the authors have made a good case for a direct link between a father’s age and the risk for his child to develop autism. Is this the only factor involved in autism? Almost certainly not. However, it can explain at least some of the increase we are seeing in autism rates.

REFERENCES

1. Abraham Reichenberg, et al., “Advancing Paternal Age and Autism,” Arch Gen Psychiatry, 63:1026–1032, 2006
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2. Lisa A. Croen, et al., “Maternal and Paternal Age and Risk of Autism Spectrum Disorders,” Arch Pediatr Adolesc Med, 161:334-340, 2007.
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3. Augustine Kong, et al., “Rate of de novo mutations and the importance of father’s age to disease risk,” Nature, 488:471-475, 2012.
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Comments

30 Responses to “Direct Evidence that a Father’s Age Affects Autism Risk”
  1. Jaymie says:

    If this were so then why isn’t all the offspring affected with some sort of autism? All the families, that I personally know, have been affected with autism have been the couple’s first born child. All the rest of the children who were born after the first born were not affected with any type of mental challenge. They did not start their families late in life either. There are two of the families where one of the parent’s have an autoimmune disease; one couple the father has Crohn’s disease and the other couple the mother has Lupus.

    One of the couples happens to be a part of our family. When there was the scare of the vaccinations we did not completely vaccinate our children due to already having a severely ADD child (our first born). Since we did not do this, now we are having problems with entering into colleges. Parents are struggling to find out what is best for their children. It seems like in the medical arena that parents scramble to find the best solutions for their children’s health care to find out it will only hurt them in the long run.

  2. jlwile says:

    Jaymie, remember that there is a lot of information in the genome. When a mutation occurs, that doesn’t necessarily mean the result will be autism or some neurological disorder. Some mutations are neutral, and even if the mutation is bad, it might not be in a part of the DNA that deals with neurological processes. As a result, increased mutations increase the risk of autism, but they don’t guarantee autism.

    Also, this analysis doesn’t tell us that all elderly fathers will produce autistic children. It also doesn’t tell us that young fathers will not have autistic children. It only tells us that the older the father is, the higher the risk of autism becomes.

  3. Jason says:

    Are you aware of any studies comparing autism rates between different countries? I do wonder if GM food and the chemicals, growth hormones, pesticides, herbicides etc don’t play a role of some kind?

    I have noticed for instance, since moving to the UK, a large amount of people are on anti-depressants. Also, many children have autism and other medical/psychological disorders. I rarely heard of children suffering from these disorders when living in South Africa. In fact as far as I know, these disorders are rare in Africa altogether.

    Could it be the food, the water or possibly genetic? What about medicines? Medicine is not readily available to South Africans and I would imagine they medicate a lot less.

    South Africans have many other health related issue to deal with, like starving to death, access to clean water and sanitation.

    Just thinking out loud Dr Wile.

  4. jlwile says:

    Jason, here is the best summary I know of autism rates around the world. As you can see, the rates vary widely. The problem is that making comparisons between countries is very hard to do because of all the different variables involved.

  5. Scott Renslow says:

    This link may be helpful for people who are interested in the vaccination/autism connection:

    http://en.wikipedia.org/wiki/MMR_vaccine_controversy

    The misconduct of Andrew Wakefield resulted in death and disease that should not have occurred.

    Are Christians more likely to fall prey to the anti-vaccine movement because they generally place less value in science (and thus generally have lower scientific literacy)? If yes, how do we correct this problem within the Christian community?

  6. cl says:

    Interesting. I have a few questions:

    1) Why was this filed under “Christian myths?”

    2) Correct me if I’m wrong, but, in the vast majority of cases (indeed some say all cases), don’t mutations bear adverse effects for offspring, as we see here?

    3) If 2 is correct, on what grounds do evolutionists credit mutations for the introduction of cumulative features so adaptive that they turned pond scum into artists, musicians and world-class thinkers?

  7. jlwile says:

    Thanks for the link, Scott. I also blogged about Wakefield.

    Your question is a good one, but probably not correct. On average, I find that Christians place more value on science than the general public. I don’t know of any studies that indicate this. I am just talking about my personal experiences. I find that Christians are generally very interested in learning about God’s creation, and they tend to follow scientific issues “for fun” more than the general public.

    I think Christians are more likely to fall prey to the anti-vaccine movement because they are very willing to be skeptical of consensus opinion. Thus, when they see anti-vaccine propaganda dressed up as science, they are inclined to be convinced by it, as it questions the consensus opinion.

  8. jlwile says:

    Good questions, cl.

    1) It is a popular Christian myth that vaccines cause autism.

    2) I would say you are wrong on that point. Most mutations are neutral. They cause neither harm nor benefit. This is because the genome has been designed so well that it is resistant to mutational degradation. Suppose, for example, a gene had the sequence thymine-thymine-thymine in it. That calls for the amino acid Phenylalanine. If the last thymine mutates to a cytosine, the sequence is now thymine-thymine-cytosine, and that still codes for Phenylalanine. Thus, the mutation didn’t cause a change in the coded protein at all!

    3) Most evolutionists would say that natural selection takes care of that. If a mutation is harmful, it is selected out of the population. As a result, a population only “keeps” the neutral and beneficial mutations. I think the key is that as far as we can tell, mutations don’t add anything novel to the genome. They can tinker with information that is already there, but they don’t add any fundamentally new information.

  9. Jason says:

    @Scott Renslow, you say “Are Christians more likely to fall prey to the anti-vaccine movement because they generally place less value in science (and thus generally have lower scientific literacy)?”

    Huh?

    How on earth did you come to this conclusion? Christians are NOT anti-science, this is Darwinist propaganda.

    Please clarify how or why you feel Christians place less value in science? Or how Christians have a lower scientific literacy than non-Christians in general?

    Thanks

  10. Jason says:

    Dr Wile, you are the expert on vaccines etc and I defer to your superior knowledge on the subject, but….

    I am still highly suspicious of vaccinations. Perhaps because I distrust “big business” and the pharmaceutical industry who promote it?

    I know you are pro-vaccination, and I usually find myself agreeing with your position on many matters, but for some reason, vaccinations give me a negative vibe.

  11. jlwile says:

    Jason, I certainly understand your distrust of big business and the pharmaceutical industry. However, you have to remember that they don’t control the scientific literature. As a result, I get my information about vaccines from the scientific literature, and the studies published therein show that the majority of vaccines are safe and effective for the vast majority of people.

  12. Scott Renslow says:

    @jlwile and @Jason, I have also experienced that Christians are generally interested in learning about God’s creation (and thus science in general). However, from my personal experience in the United States, I have not seen this translate well into actual scientific literacy. That is, deep understanding of scientific concepts, technical knowledge, and scientific thinking. Generally, Christians tend to have only a surface level understanding of science. This is from my personal experience of Christians “on average”, other people may have had a different experience and of course there are many individual exceptions to the “average”.

    Here I link to a study by Dr. Sherkat from Southern Illinois University. http://onlinelibrary.wiley.com/doi/10.1111/j.1540-6237.2011.00811.x/abstract

    I would argue that scientific literacy is a problem for the United States, and particularly for Christians.

    I do not think it is a coincidence that there is a significantly lower percentage of professional scientists that claim to be Christians compared to the population average. Is it safe to say then that Christians place lower value on science than non-Christians? I would say yes, otherwise we would see more Christians holding jobs in the sciences.

    I hope this clarifies my previous question, and addresses the comment by @Jason. To be clear, I do not think that Christians are “anti-science”. Having a low science literacy is different than anti-science. One can be very pro-science, but have a poor scientific literacy.

    What can be done to fix this problem?

  13. jlwile says:

    Scott, I don’t know the details of the study, but I get very skeptical when a study talks about measuring “scientific literacy.” I have a PhD in nuclear chemistry, have been awarded research grants by the National Science Foundation, have won awards for my original scientific research, and have published in the peer-reviewed scientific literature. However, I would score low on a lot of “scientific literacy” tests, because I don’t swallow the scientific consensus blindly. Instead, I confront the data myself and often end up disagreeing with the scientific consensus.

    I don’t see a low scientific literacy among Christians. Indeed, a Christian College recently beat out all other participating colleges on the ETS Proficiency Profile in science. However, I do see a low scientific literacy in the population as a whole. To fix that, I would suggest that scientists stop trying to push dogma and instead start trying to promote critical thinking. One way to do that is to discuss scientific controversies. Research shows that this improves science education, and I think it will make people want to learn more about science.

  14. Scott Renslow says:

    Openly discussing scientific controversies is an excellent approach to increase critical thinking and ultimately, scientific literacy. I appreciate the posts that you linked in your comment. Your ideas on promoting healthy skepticism, for example through a young-earth-creationist education, should not be ignored as changes are made to the current education system. Another solution for increasing scientific literacy is to increase early interest in the sciences through hands-on learning modules. Encouraging curiosity and exploration is best done through all of the senses. I believe that strict book learning can quickly kill curiosity and even critical thinking.

    Regarding the low scientific literacy among Christians, further research is needed. I am biased by my experience working at a national lab, where Christians are rare. How do we justify the low concentration of Christians in science-based fields? Is not the peer reviewed science literature dominated by non-Christian authors, as are both academic and non-academic science positions? Why are their so few Christians in the “elite scientists” category (i.e. fellows of the National Academy of Sciences). I will do further research sometime today to see what the peer-reviewed data says. Dr. Elaine Ecklund’s studies may be a good starting point.

  15. jlwile says:

    Scott, I am not sure anyone has ever done a census of Christians in science fields. However, I will say this: are often called to do more direct service to others, such as missionary work, the ministry, etc., etc. Even those who are science-minded might not choose scientific research as a career. Instead, they might choose the medical field, which is more related to directly helping others. Once again, I haven’t seen a census, but it wouldn’t surprise me to find an overabundance of Christians in the medical professional fields.

  16. Scott Renslow says:

    Dr. Wile, your hypothesis about Christians in the medical field made sense to me. However, it does not appear to be true.

    A study by Dr. Curlin (Religious Characteristics of U.S. Physicians) showed that the percent of physicians that claim Protestant affiliation was ~39%, and 76% said that they believe in God. Both of these were lower than the average US population (~55% Protestant, and 83% believe in God). At least according to this study, there is not an overabundance of Christians in the medical field.

    A study by Dr. Ecklund (Religion among Academic Scientists: Distinctions, Disciplines, and Demographics) showed that natural and social scientists are about 50% less likely than the average US population to be Evangelical or Protestant. But they are over 3 times likely to have no religious affiliation. Compared to other scientists, those in chemistry and political science were more likely to believe in God, whereas those in biology and physics were least likely. Several other studies corroborate these findings.

    At first, I thought that maybe the appearing trend was supporting the fact that Christians are less likely to get advanced degrees. However, the numbers do not add up:
    http://religions.pewforum.org/pdf/table-education-by-tradition.pdf
    The difference is only a few percent, which is not enough to account for the difference we see in physicians and scientists. Maybe this then: Christians are less likely to get advanced degrees specifically in science fields?

    Not to lose focus: Science illiteracy in the Christian community and lack of Christians in science-related fields is a problem that should be actively addressed.

  17. jlwile says:

    Thanks for the links, Scott. It seems that my hypothesis about Christians in the medical field is wrong. I think you are right that Christians are less likely to get advanced degrees in science. After all, a lot of Christians probably get advanced degrees in things like theology, Greek, Hebrew, and history, as those subjects are more directly related to Biblical issues.

    I still disagree with your premise. I don’t see any more scientific illiteracy in Christians than any other part of the population. I agree that scientific illiteracy in the population as a whole is a problem, and I think the best way to address that is what I mentioned before: scientists should stop trying to push dogma and instead start trying to promote critical thinking. One way to do that is to discuss scientific controversies rather than act as if they don’t exist.

  18. shevrae says:

    I can only contribute anecdotal evidence, but I’m a Christian who went into science – specifically biochemistry. I met several other Christians during my time working at a biotech company and later at a university lab. I never felt like a member of a tiny minority.

    In contrast, my husband went into engineering, and he finds very few Christians in his work environment, and that’s after years of experience in several different offices.

    Now I’m busy homeschooling 4 little girls, and doing my best to ensure that they are not only scientifically literate, but they turn out to be science geeks like me. :)

  19. jlwile says:

    I applaud your efforts, Shevrae!

  20. Vivielle says:

    Hi Scott,

    I found that interesting that you mentioned that chemists are more likely to believe in God than biologists or physicists. My experiences as a college student would certainly back that up( although merely anecdotal evidence). I’ve had bio and physics professors spout off about evolution, there not being a God etc more than once (evolution not a big surprise from the bio professors), and they’ve always tended to seem quite militant about it. I’ve never had anything like that happen in a chem class.There was actually one chem prof. who told the class that he didn’t believe in God. Until he took biochemistry.

    Anyway, your comments have been really interesting to read! I am curious though, and hope you don’t mind my asking, are you bringing this up because you are pro-Christian and think that more Christians should go into science, or because you think that Christians don’t make good scientists, or some other reason?

    -Vivielle

  21. Greg McCann says:

    Dr. Wile, I hope I am not getting too far off-topic but your statement that the pharmaceutical industry does not control scientific literature caught my eye. I also noticed that the most recent research you cited in your linked article was nearly ten years old. I am not an expert on the subject myself, but I can’t help noticing that there are a number of recent studies claiming that pharmaceutical companies do indeed suppress unfavorable research results. One of many examples is reported on here – “Drug research routinely suppressed, study authors find”:

    http://www.jsonline.com/features/health/drug-research-routinely-suppressed-study-authors-find-qd3kfnn-136625848.html

    This was just the first of many results returned by a Google search for “pharmaceutical company suppresses research”. I think you are placing more faith in the pharmaceutical companies than they deserve.

  22. jlwile says:

    Thanks for your comment, Greg. It is not too far off-topic. However, I do think you are a bit confused about the scientific literature. The studies your link discusses are the clinical trials done by the pharmaceutical companies. Of course the pharmaceutical companies control their clinical trials. After all, they pay for them. Thus, they are most certainly in control of those studies. The government is supposed to monitor the studies to make sure nothing underhanded is going on, but the government is inept in most things, so it is not surprising that it is inept in its oversight role when it comes to the clinical trials. However, the clinical trials represent only a tiny, tiny fraction of the drug-related studies in the scientific literature.

    Most of the drug-related studies in the scientific literature are monitoring studies, which are done independent of the pharmaceutical companies. For example, the story you link says, “In 2007, an independent analysis of the diabetes drug Avandia found that the drug increased heart attacks and cardiovascular deaths.” That kind of research is beyond the control of the pharmaceutical companies, and that kind of research is what confirms the safety and efficacy of most vaccines.

    Indeed, think about the British Medical Journal studies that the article you linked discusses. Do you think the pharmaceutical companies wanted those studies published? Of course not. If they controlled the scientific literature, those studies would have never seen the light of day. Neither would any of the other studies that end up costing the pharmaceutical companies millions of dollars. The very fact that we know of these cases where the pharmaceutical companies suppressed data from their clinical trials shows that the pharmaceutical companies don’t control the scientific literature when it comes to medicine!

    Please note that the studies I cite in my articles are old because I wrote those articles many years ago. As your own link demonstrates, very recent studies that are very bad for the pharmaceutical companies get published in the scientific literature. As a result, it is clear that the pharmaceutical companies don’t control the scientific literature. So I am not putting any faith in the pharmaceutical companies. I am putting faith in the proven track record of the scientific literature.

  23. No thoughts to add, but congrats to all the commenters for a great thread!

  24. cl says:

    Dr. Wile,

    Thanks for the answers way back up there at October 11, 2012 at 7:22 am. 6 days is like a year in internet-thread time, I had almost forgot about this thread :)

    By the way, why don’t you have the “subscribe” feature enabled for posts and comment threads? It might help people keep track easier. Just a polite suggestion that could only improve an already-good blog.

  25. jlwile says:

    Cl, I didn’t know it was turned off. I will try to see about turning it on.

  26. Scott Renslow says:

    Vivielle, I do not mind your question at all. It might have helped for me to clarify my own position earlier. I am a Christian myself, and thus pro-Christian. Furthermore, I am a new PhD scientist at a US national lab, and a contributor to the peer-reviewed science literature (publish or perish they say!). Like non-Christians, Christians can make both excellent or horrible scientists. I think more Christians should go into the sciences, or at least Christians should be above-average when it comes to science literacy and education. Dr. Wile and I may disagree about the state of scientific literacy in the Christian community compared to the average population, but we both agree that poor scientific literacy should be addressed for the US population as a whole.

  27. gracekalman says:

    Do you advocate waiting to give children vaccines? There is no way I am letting them give my two-month-old six vaccines in one visit. I might even wait until they are seven or eight years old. Vaccines like measles, meningitus (however you spell that), and polio seem sensible. Also, do you know if there is actually a connection between not getting chicken pox as a child and getting shingles as an adult?

  28. jlwile says:

    Grace, I don’t think waiting is necessary. However, if it makes you more comfortable, that’s fine. Giving the vaccines on a delayed schedule is better than not giving them at all. Waiting until 7 or 8 could be a problem for some vaccines, though. After all, the most important time to get vaccinated against whooping cough is while the child is an infant, as that’s when it is deadly.

    Shingles is caused by reactivation of the virus that causes chickenpox. That’s because once you get over chickenpox, the virus never goes away completely. It stays dormant and is kept dormant by the body’s immune system. But if your immune system becomes weak, it can come out of dormancy, causing shingles.

  29. gracekalman says:

    I forgot whooping cough, yes, I would get that earlier, but not before a year old.

  30. Vivielle says:

    Scott,

    Thanks for answering my question. I too am a Christian, and am finishing up an undergraduate degree in one of the physical sciences, and hope to be in graduate school this time next year. So basically, yes, I would agree that both Christians and non-Christians can be either excellent or not so excellent scientists.

    This is purely anecdotal, but I have to mention that in my college career thus far students who I know are Christians have consistently been at the top of the class in a wide range of science classes (chemistry, physics, and biology). (Obviously this is purely anecdotal and there’s more to be an excellent scientist than being at the top of the class!) Which is part of why it annoys me a great deal when people say that Christians can’t be good scientists.

    Anyway, interesting discussion and thank you for starting the conversation!

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