As men get older, they are more likely to father babies who will develop autism or schizophrenia, according to a new report that for the first time quantifies a risk widely suggested by recent studies. The culprit: genetic mutations in sperm that increase with age.
A genetic analysis of 78 families in Iceland found that the age at which a father parents his children "determines how many mutations those offspring inherit," says the cover story of the current issue of the journal Nature. The research focused on families in which a child had developed autism or schizophrenia despite neither parent showing signs of a similar disorder. The goal was to identify genetic mutations in children that were not present in their mothers or fathers.
“The older we are as fathers, the more likely we will pass on our mutations,” the study's lead author, deCODE Genetics chief executive Kári Stefánsson told Nature. “The more mutations we pass on, the more likely that one of them is going to be deleterious.”
Earlier thinking had presumed that a mother's age was a bigger factor than a father's in determining whether a child might be born with autism or other disorders. But the Icelandic study confirmed what was more recently theorized: Women are born with "their lifelong complement of egg cells," so their number of mutations remains steady throughout their reproductive lives; but men's sperm cells are "continually being generated" and, therefore, are always acquiring new, or "de novo," mutations, according to Nature.
It is these genetic mutations that influence a child's likelihood of encountering developmental issues. "The father’s age," Nature reports, "accounted for nearly all of the variation in the number of new mutations in a child’s genome." And the risk that age confers rises exponentially, according to Stefánsson's research, which suggests that a 36-year-old passes on twice as many mutations as a 20-year-old, and a 70-year-old eight times as many.
“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,” Stefánsson told The New York Times. “And it’s stunning that so little is contributed by the age of the mother.”
In Iceland, the team found, as the average age of fathers rose from 28 to 33 from 1980 to 2011, the number of new genetic mutations in newborns rose from 60 to 70.
The latest research from the U.S. Centers for Disease Control and Prevention found that 1 in 88 American children have autism spectrum disorder, a 78 percent increase since 2007. Although better diagnosis and other factors that might predispose people to autism may help explain the rise, UCLA neurobiologist Daniel Geschwind told Nature, "I think we will find, in places where there are really old dads, higher prevalence of autism."
The overall risk that a man older than 40 will pass autism or similar conditions to his children is 2 percent, which is, as the Times pointed out, "hardly reason to forgo fatherhood later in life." As the Times wrote, "the birthrate of fathers age 40 and older has increased by more than 30 percent since 1980, according to government figures, but the [autism] diagnosis rate has jumped tenfold."
University of Washington genome sciences professor Evan Eichler told the Times, “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?’ 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.”
Still, "this study provides some of the first solid scientific evidence for a true increase in the condition” of autism, Dr. Fred Volkmar, director of the Child Study Center at the Yale School of Medicine, told the Times. “It is extremely well done and the sample meticulously characterized.” De novo genetic mutations may account for as many as 30 percent of new autism cases, the new research suggests.
In an editorial accompanying the Nature article, Univeristy of Michigan evolutionary biologist Alexey Kondrashov wrote that it was logical that disorders affecting the brain were most impacted by a father's age: "This is consistent with the fact that more genes are expressed in the brain than in any other organ, meaning that the fraction of new mutations that will affect its functions is the highest."
If the link between a father's age and a child's developmental issues is further validated by additional studies, he said, "collecting the sperm of young adult men and cold-storing it for later use could be a wise individual decision.”