Future-Sayings:
In the future, the average age of fathers will continue to rise and with that the % of children who are diagnosed with autism and schizophrenia in the future will also continue to rise. Already, as many as 20-30% of cases are, in part, considered attributable to the rising tide of older fathers.
Probability Rate:
Bank on it!
Father’s Age Is Linked to Risk of Autism and Schizophrenia
By BENEDICT CAREY
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, likevaccinations, 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.”
Source:http://www.nytimes.com/2012/08/23/health/fathers-age-is-linked-to-risk-of-autism-and-schizophrenia
ORIGINAL SOURCE ARTICLE
Fathers bequeath more mutations as they age
Genome study may explain links between paternal age and conditions such as autism.
Older fathers’ sperm have more mutations — as do their children.
V. PEÑAFIEL/FLICKR/GETTY
In the 1930s, the pioneering geneticist J. B. S. Haldane noticed a peculiar inheritance pattern in families with long histories of haemophilia. The faulty mutation responsible for the blood-clotting disorder tended to arise on the X chromosomes that fathers passed to their daughters, rather than on those that mothers passed down. Haldane subsequently proposed1 that children inherit more mutations from their fathers than their mothers, although he acknowledged that “it is difficult to see how this could be proved or disproved for many years to come”.
That year has finally arrived: whole-genome sequencing of dozens of Icelandic families has at last provided the evidence that eluded Haldane. Moreover, a study published in Nature finds that the age at which a father sires children determines how many mutations those offspring inherit2. By starting families in their thirties, forties and beyond, men could be increasing the chances that their children will develop autism, schizophrenia and other diseases often linked to new mutations. “The older we are as fathers, the more likely we will pass on our mutations,” says lead author Kári Stefánsson, chief executive of deCODE Genetics in Reykjavik. “The more mutations we pass on, the more likely that one of them is going to be deleterious.”
Haldane, working years before the structure of DNA was determined, was also correct about why fathers pass on more mutations. Sperm is continually being generated by dividing precursor cells, which acquire new mutations with each division. By contrast, women are born with their lifelong complement of egg cells.
Nature Podcast
deCODE’s Kári Stefánsson explains to Ewen Callaway how a father’s age might affect a baby’s risk of disease.
00:00
Stefánsson, whose company maintains genetic information on most Icelanders, compared the whole-genome sequences of 78 trios of a mother, father and child. The team searched for mutations in the child that were not present in either parent and that must therefore have arisen spontaneously in the egg, sperm or embryo. The paper reports the largest such study of nuclear families so far.
Fathers passed on nearly four times as many new mutations as mothers: on average, 55 versus 14. The father’s age also accounted for nearly all of the variation in the number of new mutations in a child’s genome, with the number of new mutations being passed on rising exponentially with paternal age. A 36-year-old will pass on twice as many mutations to his child as a man of 20, and a 70-year-old eight times as many, Stefánsson’s team estimates.
The researchers estimate that an Icelandic child born in 2011 will harbour 70 new mutations, compared with 60 for a child born in 1980; the average age of fatherhood rose from 28 to 33 over that time.
Previous studies have shown that a child’s risk of being diagnosed with autism increases with the father’s age. And a trio of papers3–5published this year identified dozens of new mutations implicated in autism and found that the mutations were four times more likely to originate on the father’s side than the mother’s.Most such mutations are harmless, but Stefánsson’s team identified some that studies have linked to conditions such as autism and schizophrenia. The study does not prove that older fathers are more likely than younger ones to pass on disease-associated or other deleterious genes, but that is the strong implication, Stefánsson and other geneticists say.
The results might help to explain the apparent rise in autism spectrum disorder: this year, the US Centers for Disease Control and Prevention in Atlanta, Georgia, reported that one in every 88 American children has now been diagnosed with autism spectrum disorder, a 78% increase since 2007. Better and more inclusive autism diagnoses explain some of this increase, but new mutations are probably also a factor, says Daniel Geschwind, a neurobiologist at the University of California, Los Angeles. “I think we will find, in places where there are really old dads, higher prevalence of autism.”
However, Mark Daly, a geneticist at Massachusetts General Hospital in Boston who studies autism, says that increasing paternal age is unlikely to account for all of the rise in autism prevalence. He notes that autism is highly heritable, but that most cases are not caused by a single new mutation — so there must be predisposing factors that are inherited from parents but are distinct from the new mutations occurring in sperm.
Historical evidence suggests that older fathers are unlikely to augur a genetic meltdown. Throughout the seventeenth and eighteenth centuries, Icelandic men fathered children at much higher ages than they do today, averaging between 34 and 38. Moreover, genetic mutations are the basis for natural selection, Stefánsson points out. “You could argue what is bad for the next generation is good for the future of our species,” he says.
- Nature
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- doi:10.1038/488439a
