I wonder how much of the mutations in genetic material relate to simply aging and how much of it might be a reflection of environmental exposures based on when the father was born? Substances like mercury or lead spring to mind as things that someone just 10 years older than myself would have likely had much more exposure to despite living in the same place and having the same socioeconomic status.
The fact that the female-contributed genetic material error rates are static might speak to this effect to some degree. I wonder if they are studying autism diagnosis going back in time or if all the autistic children were around the same age.
In other words, these results are statistically significant, but not clinically significant.
There are entire industries that depend on you not knowing the difference between these two concepts, which makes it all the more important that you actually learn it.
Yes. For something to be statistically significant means there is some difference between the two groups that is most likely not attributable to random chance. For something to be clinically significant means the difference between the two groups is large enough to have noticeable health effects or impact one's decision-making about medical issues.
In the book The Emperor's New Drugs, about the efficacy of anti-depressants (or lack thereof), Kirsch gives the example that if you had a group of 500,000 people and found that smiling frequently increases life expectancy by 10 seconds on average, this may well be statistically significant because the study population is so large. However, it's not clinically significant because no one really cares if they live an extra 10 seconds, certainly not enough to change some major aspect of their behavior at least.
In this case, if the chances of having kids with autism or schizophrenia increase by/to? at most 2%, as the article states, then in practice this shouldn't really deter anyone from having kids. Thus, while the findings are statistically significant, they are not clinically significant.
"I think 2% is actually a very high risk for something with rather severe consequences."
Keep in mind that the overall risk of autism is 1 in 88, or 1.1%, and the overall risk of schizophrenia is about 1%. So it's not like you get a free pass if you have kids earlier. Also, there are other benefits to having a child later in life in terms of things that benefit the child, even if there are more neurodevelopment risks and disadvantages at the biological level.
Sure, I just meant in general 2% seems very high. Friends of mine got the suggestion to do a test with a 3% chance of killing the embryo (or what they call it - it was rather early stage). The doc apparently thought nothing of it. I thought it is crazy (and they thought so too). Added information that the mom was already 40, so not that many new attempts left.
So is clinical significance determined in part by perceived significance? I feel that a potential 2% risk of conditions as serious as those mentioned in the article could easily influence some people towards choosing to have kids at a younger age.
"So is clinical significance determined in part by perceived significance?"
It's determined entirely by perceived significance. For each type of drug, there is usually some agreed on metric within the field that determines what constitutes clinical significance. E.g. a blood pressure drug might have to lower blood pressure by 5% or 10% or whatever. And often times the metric isn't even relevant, as in the case of a reduction in blood pressure vs. a reduction in total mortality / morbidity.
However, at the end of the day what the academic community considers clinically significant doesn't really matter, it's your own preferences and values that should be your guide. Especially since in practice everyone is basically out to trick you in order to make more money, from pharma companies to newspapers to academic journals to professional organizations (AMA, APA, etc.), etc. That's why it's important to really understand this stuff forwards and backwards and to keep your wits about you.
That's certainly how I hear it, too. I've never heard a woman expressing fear that she might have waited too long, such that her child will get Downs. Rather, fear that she might have simply waited too long, and now it is too late.
I'm over 40, and I certainly have! Downs can be detected in time for an abortion, but it means that you have to get pregnant all over again, and risk Downs and the various other bad mutations again, and risk miscarriage for whatever reasons all over again, etc.
So for non-fundamentalist women, there is fear of having a Downs child, but it gets rolled into the package of "worried about getting to have a successful pregnancy at all".
I am guessing, since the article you link doesn't actually link to the scientific study, that it is referring to: http://pediatricbioscience.com/publications/pdf/Pub16.pdf This did not examine any form of causality, as the currently-linked study did, nor did it evaluate the children themselves. By not controlling for evaluation mechanisms, the study you link only addresses patterns of early diagnosis and treatment. While it is interesting, the researchers themselves say that the data is hardly conclusive. The current study, on the other hand, explores not just correlation but causation, and thus is far more persuasive.
Second, you are comparing increase in risk to total overall risk. The percentage increase for men going from age 25 to 40 is 110%, not 2%. The study you link found a comparable number for women over age 40 of 0.4%.
The article doesn't directly mention the risk to a man in his 20's or 30's... just that up to 30% of the cases of autism has to do with the mutations associated with "older" sperm. Obviously there is a lot more work that needs to be done to understand this, but it would be nice if they presented this information in a more actionable form.
Mine was 44 and having lost my (adopted; non-biological) mother to Alzheimers, I've seen firsthand how that goes down. Needless to say, I'm pretty freaked out about that possibility.
This is the third such study published within this year. The difference being that this study did full genome sequencing rather than exome (regions coding for proteins) sequencing.
The other papers:
O'Roak BJ, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. 2012
Sanders JS, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012
These are disorders that effect a person's personality, which could mean all sorts of new variables to control for. A man who has mild symptoms of autism or schizophrenia may well take longer to establish himself in his life and have children.
the decision of people to have children late is harmful to society in a number of ways.
i know an "irresponsible" woman who had a child when she was a teenager. she was 40 when her child was in college and ready to move on in her life. if she lives until 80, she'll share 60 years of experiences with her child on average.
if some professor decides to wait until they have tenure (say 40) before they have kids, they're likely to have 40 years of overlap. they'll be dealing with an unruly adolescent when they are 55.
if you have a kid at 50 (some people do!) then you have 30 years of overlap and you're dealing with an unruly teenager at 65!
(Oddly, have kids at 30, like I did and my dad did, and you're in your 40s when your kids are in their teens. The 40s seem to be a time that parallels adolesence and a number of ways... Stan Lee and Mike Ditko were in their 40's when they were imagining the adventures of teen Peter Parker...)
so having kids late in life means that parents have less experience with their children and children get less out of their parents.
(note that smaller nuclear families have an almost genocidal effect on extended families... if you have N siblings on average, you have N^2 cousins!)
for years i've believed that late childbearing has an effect similar to an increase in background radiation, this study confirms that and just adds to the case
It's not just your own values, it's the effect that your values have on civilization as a whole.
I see civilization as a race between our ability to create problems and our ability to solve problems.
You can make a case that a high reproductive rate is a social danger because it causes resource depletion and overall causes us to develop problems faster just because more people make more problems.
On the other hand, a low reproductive rate makes problems too. It's much easier to fund the kind of welfare state that the left wants when we have a high reproductive rate. The dreams of the right, in which many of us can save money in individual accounts and enjoy an easy retirement, are also dashed by a low reproductive rate.
Honestly I don't know what the optimal reproductive rate is. But I think there is something more to life than the quality and quantity of your orgasms, what pleasure you get, and the self-aggrandizement you experience making other people rich and famous.
Quite a few people have worked hard to create the civilization we have, and in particular, two parents invested a lot to raise me. I think it's fair to "pass this forward" and expect that we all produce (on average) a child each and that that's just a part of the mission we have on planet Earth.
That's just your opinion that having children when older is harmful to society. But what I consider more harmful to society is this thinking that every single individual action has to be weighed against the "benefits of society". This thinking seems to be more and more prevalent and is dangerous for freedom.
As a subtle rhetorical way to suggest that OP should maybe get over himself.
Our purposes aren't objective. They are ours to choose, as individuals. Other animals may live only to propagate their genome, but as humans, our societies appear to function best when we convince ourselves that we're here to accomplish things other than reproduction alone.
We know that whatever damage is caused, it can't be too bad because children born using sperm donors - which can be frozen for storage - don't have increased defect rates, but have decreased defect rates, something like 1/5
Correct me if I'm wrong... but this is just a study which finds a correlation. While the article hints at causation, does the study actually find that?
A scientist might say, "There is evidence of causation."
Typically in scientific research, to assert causation three things must be true: 1) Correlation, 2) Temporal ordering (for A to cause B, A must come before B), and 3) Sufficient theorizing, in other words, a plausible explanation, typically based on previously accepted research.
In the best settings, random samples from a population with a treatment condition and a control condition are the best evidence. That's not possible in an age-base study, as randomly selected groups are not treatable with "age", and even if it were somehow possible, it probably wouldn't be ethical to do so.
Unfortunately, some of the most important research can't be done with this sort of A/B test.
Consequently, assertions of causation are sometimes incorrect. But that's true with any research methodology. Know that the question of causation is something the scientific community wrestles with, and a moderately informed population shouting "correlation != causation", while typically a good response to a newspaper article, isn't always the most helpful with regard to a scientific journal.
What would "actually find that" mean to you in this context? Science is not as clean and perfect as many would like to imagine. A strong correlation and a plausible biological mechanism combined are about as strong evidence as is possible.
People who have children later in life are going to have a number of significant demographic difference from those who have children earlier.
Here's how you rule out each possibility: for each one, you pair up people in the "earlier" and "later" groups who have identical demographics. If the subgroups have identical outcomes, you have found the cause. If not, you have eliminated a cause.
That still doesn't "prove" causation, as there are innumerable demographics that are either impossible to match or nobody thinks to match. And FWIW, the paper does say that "factors other than father’s age do not seem to contribute substantially to the mutation rate diversity in our data".
> "factors other than father’s age do not seem to contribute substantially to the mutation rate diversity in our data".
But as another poster already pointed out, age could be hiding other factors.
Exposure to environmental factors that could cause mutations change with time, e.g, older fathers would have been exposed to pesticides that were banned before younger fathers were born, nutritional changes, etc...
Mutations can also be beneficial. I wonder if other traits, such as intelligence variability, are also related to father age?
There's even a nice evolutionary coincidence: if you wanted to play with genes to make something, it's a good idea to start with the genes of older fathers, because they've shown they can survive longer.
Biologically, this makes sense. A woman is born with all her eggs already in her ovaries, while men manufacture sperm on demand. Obviously, the consequences of accumulated genetic damage can only manifest in the latter case.
From the first sentence: "because of random mutations that become more numerous with advancing paternal age".
From the sixth paragraph: "The research team found that the average child born to a 20-year-old father had 25 random mutations that could be traced to paternal genetic material. The number increased steadily by two mutations a year, reaching 65 mutations for offspring of 40-year-old men."
What? It seems that there is a mechanism proposed, that is increased mutations in older men.
Secondly, I think it's hardly useful to state that discoveries without mechanisms are useless. Certainly, having the mechanism is more useful, but having the correlation itself is valuable data. Or else the "law of gravity" would have been useless for a couple centuries.
This specific case, this specific correlation, is not really ready to go into the popular press as headlines for the general public to take home.
It is easy to do controlled experiments regarding gravity which are not completely loused up with confounds. Nobody needed to go data-fishing in order to find gravity - it's a very clear and strong phenomenon.
Are you sure that there are no possibly relevant systematic differences OTHER than age, between men who have children early and ones who have children late?
A 'proposed' mechanism cannot substitute for understanding of what is actually happening, in the context of popular publication of data suggesting that autism is caused by having babies too late... this is a month away from the women's magazines and two months from parents being blamed for their children's autism. It would be more responsible to actually demonstrate a causal link before running to the presses.
I believe that the complaint is that the mechanism is something of a dodge. To put it differently, the Barry Allen can run faster than the speed of light. If you asked my why he can violate special relativity, I'd tell you that he was in a lab accident. That's the mechanism by which he went into a state where he was able to travel at superluminal velocity. However, that explains absolutely nothing about why he's violating special relativity.
In the same way, increased mutations in the paternal DNA does explain why something weird would happen with the offspring. However, it does nothing to explain why that something weird manifests itself as autism.
This has been "known" for years with autism, based on observational data. Normally, I don't put much into observational data, since it can be so wrong, but in the autism/paternal age case, you have a HUGE, HUGE leap in likelihood of autism based on father's age. A man in his 40's is thousands of times more likely to have an autistic child than a man in his 20's, as a I recall from previous observational data.
This is the sort of thing you should check before you post. It only took a minute to find a well-sourced overview of the clinical literature on wikipedia, with results clustering around a 40% increased risk of autism for the offspring of men in their forties (vs men in their twenties), though one study from Israel found the the risk to be almost 6 times higher.
To blithely suggest that the probability is 'thousands of times' higher is misleading to the point of irresponsibility. Think of the confusion and anxiety such misinformation can create in the mind of an uninformed reader.
I think you may be thinking of the relationship between down syndrome and maternal age, which I have heard estimated at "thousands of times more likely". However, perhaps this is a slight exaggeration as well:
The fact that the female-contributed genetic material error rates are static might speak to this effect to some degree. I wonder if they are studying autism diagnosis going back in time or if all the autistic children were around the same age.