Father's age linked to autism

Risk of genetic mutations tied to autism may increase with each year of father's age

The father's age may matter more than the mother's when it comes to the risk of some disorders like autism in children.

A new study shows the number of "de novo" or new genetic mutations passed to children increases with every year of the father's age at the time of conception. And fathers pass along a greater number of these to their children than do mothers.

Researchers found the number of de novo mutations in children increases by two for every year of the father’s age. The whole amount doubles every 16.5 years.

That means a 36-year-old man passes along twice as many mutations in his sperm to his children, compared to a 20-year-old.

Previous studies have already linked these mutations to autism and schizophrenia and a variety of other developmental disorders. This study helps to quantify the potential risk.

Researchers say the findings have important implications for family planning as well as the recent rise of developmental disorders, especially autism.

“It's very likely that the increase in autism in our society of late is at least partly explained by the increase in average age of fathers,” says researcher Kari Stefansson, MD, PhD, CEO of deCODE Genetics in Reykjavik, Iceland.

“We have in many ways been led a bit astray when it comes to the impact of the age of parents,” Stefansson says. “As a society, we have been focused on the age of the mother as being detrimental, but probably the age of [the] father is more dangerous.”

Paternal Age Accounts for a Lot

The study, published in Nature, compared mutation rates in 78 Icelandic parent-offspring trios. Among the group, 44 of the children have autism spectrum disorder and 21 have schizophrenia.

Specifically, researchers looked at de novo mutation rates across the group. Researchers say these new, non-inherited genetic mutations are important for evolution and generating diversity, but they also contribute to disease.

The results showed that not only did de novo mutations increase by two for each year of the father’s age, but nearly all variation in the number of these mutations was attributable to paternal age.

“Ninety-seven percent of the difference is accounted for by the age of the father,” says Stefansson. “That was surprising to us because that means hardly anything else contributes to it.”

For example, Stefansson says, the environment may still affect the father’s mutation rate as an individual. But when you look at the population as a whole, 97% of the difference in the number of these potentially dangerous mutations is caused by paternal age.

Researchers say the next step is to better understand exactly how these de novo mutations contribute to various diseases.

While the mutations are currently associated with disorders like autism and schizophrenia, Stefansson says there could be a lot more.

Older Dads 'Mutational Bombs?'

Experts say the results underscore the fact that fathering children at an advanced age is not without risk.

“This is a breakthrough article,” says Harry Fisch, MD, clinical professor of urology and reproductive medicine at Weill Cornell Medical College of Cornell University. “It’s a real paradigm shift in terms of how we think about fertility and genetic abnormalities.”

“We used to think men can wait as long as they want to have children, but that’s not true,” he says. “Not all men can have children when they get older. If they do, they stand a higher risk of having a child with a genetic defect.”

Fisch says for women the age of 35 has become a benchmark for when the risk of having children with a genetic condition, such as Down syndrome, starts to escalate.

Now men have a reference point.

“For the first time, you can say there is a doubling of the mutation rate every 16 years,” says Fisch.

Stefansson even calls older men’s sperm “mutational bombs.”

Bottom line, Fisch says the study "is going to affect how we think about the causes of the increasing incidence of schizophrenia and autism, particularly autism.”

Previous studies have also shown that advanced paternal age is associated with a higher risk of miscarriage as well.

“As men are getting older, we are increasing the chance of genetic abnormalities in their children,” says Fisch. “It’s a public health concern.”

SOURCES: Kong, A. Nature, Aug. 23, 2012.Kari Stefansson, MD, PhD, CEO, deCODE Genetics, Reykjavik, Iceland.Harry Fisch, MD, clinical professor of urology and reproductive medicine, Weill Medical College of Cornell University, New York City.News release, Nature Journals.Veltman, J. Nature Reviews Genetics, August 2012.

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