Father’s Age Linked to Risk of Autism and Schizophrenia

Older men are more likely than young ones to father a child who develops autism or schizophrenia, because of random mutations that become more numerous with advancing paternal age, scientists reported on Wednesday, in the first study to quantify the effect as it builds each year. The age of mothers had no bearing on the risk for these disorders, the study found.

Experts said that the finding was hardly reason to forgo fatherhood later in life, though it might have some influence on reproductive decisions. The overall risk to a man in his 40s or older is in the range of 2 percent, at most, and there are other contributing biological factors that are entirely unknown. But the study, published online in the journal Nature, provides support for the argument that the surging rate of autism diagnoses over recent decades is attributable in part to the increasing average age of fathers, which could account for as many as 20 to 30 percent of cases. The findings also counter the longstanding assumption that the age of the mother is the most important factor in determining the odds of a child having developmental problems. The risk of chromosomal abnormalities, like Down syndrome, increases for older mothers, but when it comes to some complex developmental and psychiatric problems, the lion’s share of the genetic risk originates in the sperm, not the egg, the study found.

Previous studies had strongly suggested as much, including an analysis published in April that found that this risk was higher at age 35 than 25 and crept up with age. The new report quantifies that risk for the first time, calculating how much it accumulates each year. 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. The average number of mutations coming from the mother’s side was 15, no matter her age, the study found. “This study provides some of the first solid scientific evidence for a true increase in the condition” of autism, said Dr. Fred R. Volkmar, director of the Child Study Center at the Yale School of Medicine, who was not involved in the research. “It is extremely well done and the sample meticulously characterized.”

The new investigation, led by the Icelandic firm Decode Genetics, analyzed genetic material taken from blood samples of 78 parent-child trios, focusing on families in which parents with no signs of a mental disorder gave birth to a child who developed autism or schizophrenia. This approach allows scientists to isolate brand-new mutations in the genes of the child that were not present in the parents. Most people have many of these so-called de novo mutations, which occur spontaneously at or near conception, and most of them are harmless. But studies suggest that there are several such changes that can sharply increase the risk for autism and possibly schizophrenia — and the more a child has, the more likely he or she is by chance to have one of these rare, disabling ones. Some difference between the paternal and maternal side is to be expected. Sperm cells divide every 15 days or so, whereas egg cells are relatively stable, and continual copying inevitably leads to errors, in DNA as in life.

Still, when the researchers removed the effect of paternal age, they found no difference in genetic risk between those who had a diagnosis of autism or schizophrenia and a control group of Icelanders who did not. “It is absolutely stunning that the father’s age accounted for all this added risk, given the possibility of environmental factors and the diversity of the population,” said Dr. Kari Stefansson, the chief executive of Decode and the study’s senior author. “And it’s stunning that so little is contributed by the age of the mother.” Dr. Stefansson’s co-authors included C. Augustine Kong of Decode, and researchers from the University of Iceland, Aarhus University in Denmark and Illumina Cambridge Ltd. Dr. Stefansson said it made sense that de novo mutations would play a significant role in brain disorders. At least 50 percent of active genes play a role in neural development, so that random glitches are more likely to affect the brain than other organs, which have less exposure.

In the end, these kinds of mutations may account for 20 to 30 percent of cases of autism, and perhaps schizophrenia, some experts said. The remainder is probably a result of inherited genetic predisposition and environmental factors that are the subjects of numerous studies. Dr. Stefansson and other experts said that an increase in the average age of fathers had most likely led to more cases of autism. Unlike other theories proposed to explain the increase, like vaccinations, it is backed by evidence that scientists agree is solid. This by itself hardly explains the overall increase in diagnoses, at least in the United States. The birthrate of fathers age 40 and older has increased by more than 30 percent since 1980, according to government figures, but the diagnosis rate has jumped tenfold, to 1 in 88 8-year-olds. And it is not clear whether the rate of schizophrenia diagnosis has increased at all in that time.

Nonetheless, if these study findings hold up and extend to other brain disorders, wrote Alexey S. Kondrashov of the University of Michigan, in an editorial accompanying the study, “then collecting the sperm of young adult men and cold-storing it for later use could be a wise individual decision.” That very much depends on the individual. “You are going to have guys who look at this and say, ‘Oh no, you mean I have to have all my kids when I’m 20 and stupid?’ ” said Evan E. Eichler, a professor of genome sciences at the University of Washington in Seattle. “Well, of course not. You have to understand that the vast majority of these mutations have no consequences, and that there are tons of guys in their 50s who have healthy children.”
Article Published in the NYtimes. Submitted by MissMannah. Thank you!


MaryPoppin'Pills said...

When I Published this all of the links were working. When I checked back later, some were sketchy... if you have any problems, just go to the original link for the New York Times Article which is provided at the bottom of this posting for you. Thanks!

Bethany said...

Very interesting. Thanks for submitting Mannah.

Village said...

If you don't understand evolution, well never mind then.

MissMannah said...

You're welcome. I was very excited when I came across this.

Village, I don't really know what you mean by your comment. Would you care to elaborate?

RBTC said...

i am not sure if this is what village means but the post sounds like the work of Dr. Leonard Sax "The future of ( child ) men "

There are alot of environmental factors not good for guys

in any case this article can go far for explaining why autism has spiked so badly

Village said...

I was being pretty straight foward. Evolution exists whether one understands it or not. That's all.

MissMannah said...

Well yes, I got that much from your post. But I don't see how it is relevant to the article. Are you saying that the resulting autism is nature's way of telling man not to wait so long to have babies? A sort of survival of the fittest as far as age is concerned?

Nadia said...

I'm kind of confused by Villages comment, too - and wish she'd elaborate.

VIP said...

I was trying not to go there, but if we must.

The so called Creationists don't "believe" in evolution, despite the fact it's in the Bible. (What the (*)(*) do they think go forth and multiply means? God CREATED evolution.)

None is so blind as s/he who refuses to see. I refer to those so undereducated that they cannot grasp evolution as not having an understanding of evolution, rather than the ridiculous "believe" as evolution is a matter of fact not a matter of faith.

Village said...

My iPad corrected to VIP and I missed it. Sorry.

Tales from the (Nanny)Hood said...

Village, count me among the confused as well. I don't get the link between creationism and the article. What I read indicated that new research shows a possible link between parental age at conception and autism/schizophrenia. I didn't see that the researchers laid the huge autism spike at the feet of delayed paternity, nor did I see anything about creationism and/or evolution.

And I really don't get how "go forth and multiply" relates to evolution - I always saw that as a directive to make more people. :-)

And just to explain my position on the creationism/evolution spectrum, I believe that God created everything over a LONG period of time, which was turned into "7 days" by those who wrote the bible. I don't believe a "day" has meaning to God or the Creator or whatever you wish to call the being that made the universe.

Hope you'll clarify a bit moire fully!

Tales from the (Nanny)Hood said...

Arrggh! Parental = PATERNAL

ncnanny said...

Ok, we have 3 very smart well-known nannies on board here that are questioning villages comment, so gladly I can say; color me confused also!

nycmom said...

Speaking strictly as a doctor and psychiatrist, following this research closely, I too am completely confused by Village's comment.

I agree with her thoughts on evolution. However, I fail to see how they relate to the OP.

Perhaps she is saying that if one does not believe in evolution, then one would disregard the concept of our genes mutating with aging since that is a tenet requiring some belief in evolution (as it relates to natural selection, fitness, and propagation of the species)?

Or perhaps she simply means that a Creationist is going to generally disregard evidence-based medicine due to their strong faith in God as the mediator of all challenges we face -- from being born with a mental or physical disability all the way to which challenges a child born to parents of any age will face. Sort of a pre-determined fate vs. free will argument? But frankly, I am grasping at straws based on the limited information she provided.

I would love an interesting discussion on this issue for a nice change of pace on here! It would be even more enriching with someone as seemingly rational and passionate as Village usually presents, among the other bright folks on here.

Urging nanny said...

VILLAGE-speak up NoW OR forever hold your peace!

MissMannah said...

I'm glad I wasn't the only confused one!

Village, please explain further. I also would like to get into a rational discussion about this. (Not a Creationism vs Evolution, only one of us can be right sort of argument.)

Village said...

Reproduction IS evolution. Genes are shuffled, and mutations occur with every conception. Mutations are how we evolve. Scientists are decoding evolution through DNA. We literally are our mutations. A mutation which caused a brain fold is what made Homo Sapiens smart enough to create language, build, be who we are today. (There may have been two separate brain folds.) A mutation is what caused menopause, which allowed the next generations to have higher survival rates because grandma was looking after the kids. No other animal has menopause. A SINGLE letter mutation lead to Caucasians, and another single letter mutation lead to Asians. (We originated in Africa, east Africa, probably today's Kenya, from one African tribe that yelled road trip, and walked to what is today Indonesia, and then walked back. The trip is estimated to have taken 60,000 years.) The genome is made of four letters which are constantly being shuffled. Out of sequences of billions of letters, a single letter shift lead to something so profound as a new race, twice.

See why I didn't want to go down this road? Evolution is very simple and very complicated at the same time. But at the end of the day, sex is evolution. We must reproduce to survive. There have been about 30 species of humans, at present count, and our species, Homo Sapien is the only one left. We are literally the last of our species. I think it's because the male Homo Sapien thinks about sex pretty much all the time. It's probably the single greatest reason we survived and the others didn't.

Now to autism. The study showed that women have about 15 mutations that stay level throughout their reproductive years. With men however, their mutations rise as they get older, and it appears that one or several of these mutations that occur in older men leads to autism. If older men with more mutations are fathering babies, we are going to have more babies with more mutations. We have known older parents tend to have Down babies, and it appears autism is similar in origin, again, in that older fathers have more mutations. Do you follow me? It's frickin' complicated. And there appears to be several types of autism mutations as some children are non verbal while others are very smart but lack social skills. That's a HUGE range.

Do you seriously have any more questions? See why I was making a joke? If you don't understand evolution well never mind then. The whole article on autism is based on evolutionary genetics. Those so called Creationists engage in evolution when they have children. That's what makes it so funny to me.

I'm not a scientist, I just play one on ISYN. I picked up most of this at the dinner table as I come from a family of scientists. My father researched genetics. This is a layman's perspective, particularly the road trip part. Why one out of 800 tribes decided to walk to Asia is a mystery, (probably had to do with food, or lack of it) but I can imagine somebody yelled road trip if I want to.

And thanks for the rational and passionate. I'll take it. Love being rational, and I am a natural redhead. Please people, let this rest. Don't punish me anymore for making an inside the ballpark joke. I promise I won't do it again. I was just being funny, or trying to, and evolution is such a hot button issue, I truly don't want to offend.

Nadia said...

Thank you for the HUGE elaboration Village! ;-)

MissMannah said...

"No other animal has menopause."

Not true. I raise female rats and I can assure you that they experience menopause between 14 and 18 months, which is more or less their middle age. I can't speak for other animals though.

Thank you for elaborating, for the most part I completely agree with you.

It will be interesting to see if scientists think they can isolate these genes and possibly stop them from mutating.

Village said...

Every conception shuffles the genes and mutations occur. It sounds like your rats have a mutation that is causing them to stop breeding. That doesn't necessarily mean all rats have that mutation.

At the moment it is estimated that each human gene shuffle produces 4 significant mutations. One of mine is a 135 degree off axis left eye, but that doesn't mean a parent had it or a child will.

Not all mutations are passed on.

MissMannah said...

They have never bred. But rats have very apparent signs when they are in heat so I can tell when they aren't going into heat anymore. There are other animals that experience menopause:

"Menopause has been observed in several species of nonhuman primates,[3] including rhesus monkeys,[107] and chimpanzees.[108] Menopause also has been reported in elephants,[109] short-finned pilot whales[110] and other cetaceans,[111] as well as in a variety of other vertebrate species including the guppy,[112] the platyfish, the budgerigar, the laboratory rat and mouse, and the opossum, as well as some whales.[113] However, with the exception of the short-finned pilot whale, such examples tend to be from captive individuals, and thus they are not necessarily representative of what happens in natural populations in the wild."

I'm not being insistent simply because I like to be right. You just appear to be misinformed about this.

Also interesting because I have a male and a female platyfish together and I always wondered why they haven't bred, perhaps the female went through menopause before I got her.

nycmom said...

Yes, Village, I agree. Natural selection as described by Darwin relies upon mutations for us to progress via evolution. Thanks for clarifying!

RBTC said...

really interesting village - make some inside jokes anytime !