Autism risk for children with older fathers

Babies of older fathers are more likely to carry genetic mutations than those of younger fathers.

And the mutations could lead to illnesses such as autism and schizophrenia in later life, a landmark study has shown.
Scientists have, for the first time, counted the number of new mutations linked with a father's age at the time of conception and have concluded that older men are significantly more likely to have children with potentially harmful genetic changes.
The results could explain previous studies showing that certain mental and developmental illnesses with strong genetic components tend to be more common among people whose fathers were older at the time of conception.
Although the age of a child's mother has been linked with problems associated with chromosomal defects, such as Down's syndrome, there has been scant information about the contribution made by older fathers to the future health of their offspring.
"These observations shed light on the importance of the father's age on the risk of diseases such as schizophrenia and autism," the researchers say in their study published in the journal Nature. The scientists found that a new-born baby's genome contains around 60 new small-scale mutations compared with its parents and that the actual number of new mutations carried by each child was strongly dependent on the age of the father, rather than the mother, at the time of conception.
The researchers, led by Augustine Kong and Kari Stefansson of deCode Genetics in Reykjavik, calculated that a 20-year-old father transmits about 25 new mutations to his child while a 40-year-old man will pass on 65.
This means that for each additional year in the age of a father, there are, on average, two extra mutations passed on to the child. By contrast, the scientists found that the number of mutations transmitted by the mother was always about 15, regardless of her age. Alexey Kondrashov, an evolutionary geneticist at the University of Michigan at Ann Arbor, who was not involved in the study, said that the results could at least partly explain the recent rise in autism given the modern tendency for men to become fathers later in life.
"Although most of these mutations will, on their own, have only mild effects, collectively they could have a substantial impact on health," Professor Kondrashov said.
"It seems that multifactorial disorders that result from impaired brain function, like autism, schizophrenia, dyslexia and reduced intelligence, are particularly susceptible to the paternal-age effect."
Allan Pacey, chairman of the British Fertility Society, said that it was a surprise to see from the study that men transmit a higher number of mutations to their children than women and that the link with older fathers could explain the higher risks of certain genetically linked illnesses.
"Whilst not wanting so scare the children of older fathers, information like this is important to understand and should remind us that nature designed us to have our children at a young age. If at all possible, men and women should not delay parenthood if they are in a position not to," Dr Pacey said.
Professor Richard Sharpe, a male fertility specialist at the University of Edinburgh, said there is a relatively simple explanation given that men are constantly renewing their sperm cells throughout life, which means that new mutations will tend to accumulate with age, whereas women make do with the egg cells they are born with.
"The price is paid by their children because the older your father at conception, the greater the number of gene mutations you inherit from him," Professor Sharpe said.
This latest study analysed the entire genomes of 78 Icelandic families.
A spokesman for the National Autistic Society said: "While there is evidence to suggest that genetic factors may play a role in some forms of autism, there are many 'younger' fathers who have children with the condition.
"Far more investigation needs to be done into the connection between genetics and autism before we can draw any reliable conclusions."

August 23, 2012 12:09 PM Older fathers more likely to pass on autism-linked genetic mutations to offspring, study shows comments 1More+ EmailFacebookTwitterLinkedInDigg.PrintDeliciousRedditStumbleuponGoogle Bookmarks.... By Ryan Jaslow Topics News ,Kids and family ,Men ,Research . (Credit: istockphoto) (CBS News) The older a new father is, the greater chances his child may develop autism, new research suggests. Previously-held perception says older mothers are more likely to have children with autism. Though risk has been shown to increase with maternal age, some have suggested that link is overblown. Now the new study adds more clues to the ongoing mystery of what cases autism and suggests the rise in autism rates may in fact be tied to more dads deciding to wait longer to have children. Complete Coverage: Autism Awareness Study: Father's age a likely factor in autism Common myths about having a child later in life "It is of interest here that conventional wisdom has been to blame developmental disorders of children on the age of mothers, whereas the only problems that come with advancing age of mothers is a risk of Down syndrome and other rare chromosomal abnormalities," study author Dr. Kari Stefansson, CEO of deCODE Genetics, said in a press release. "It is the age of fathers that appears to be the real culprit." Several studies have found links between autism and a greater presence of certain genetic mutations. For the new research, scientists at deCODE Genetics in Reykjavik, Iceland kicked off one of the largest genome studies ever. They examined associations between conditions like autism and schizophrenia and genetics to find out what leads to mutations. The researchers sequenced the whole genomes of 78 Icelandic families with offspring who had been diagnosed with autism or schizophrenia, then sequenced the genomes of an additional 1,859 Icelanders from the general population to provide a comparison group. Their analysis showed every one-year increase in a father's age correlated to a two mutation-per-year increase in the child. Fathers in the study were an average age of 29.7 years old. A father's age could account for 15 to 30 percent of cases of autism - and an increase in schizophrenia as well - the study showed. Stefannson told Nature News that a 36-year-old would pass on twice as many mutations to his child as a 20-year-old new father, and a 70-year-old would pass on eight times as many. The findings were published August 23 online in the journal Nature. Their scientists also reported finding offspring mutations that had previously been implicated in both conditions, in addition two identifying two new genes - CUL3 and EPHB2 - which were tied to mutations in the autism-parent group. "Our results all point to the possibility that as a man ages, the number of hereditary mutations in his sperm increases, and the chance that a child would carry a deleterious mutation that could lead to diseases such as autism and schizophrenia increases proportionally," Stefansson said. Dr. Cathy Lord, director of the Center for Autism and the Developing Brain at Weill Cornell Medical College and New York Presbyterian Hospital in New York City, told CBS This Morning that these is general deterioration in genes as people age. With fathers, those mutations occur more often in men's sperm and are more likely to be passed onto to their children - and maybe one of those mutations is associated with autism or schizophrenia. Dr. Delores Maldespina, a psychiatrist at NYU Langone Medical Center, told CBS Evening News that she finds the research eye opening. "This study shows that new mutations are frequent enough as men age that fathers aging alone can explain the increase for the risk of autism," she said. "When these diseases present without a family history, the origin is in the sperm of the man and that the risk goes up as the man ages." The country's autism rate in March rose 25 percent to one out of 88 children (previous rate was one in 110), with some experts theorizing the rate may be due to improved diagnosis or environmental factors. The number of men 40 and older who father a child has increased by more than 30 percent since 1980, the CBS Evening News reported. But Yale researcher Dr. Stephan Sanders warned it's too soon to definitively say the father's age is the top factor. "So I think it is fair to say increasing father's age does increase the instance of autism but that effect is small," Sanders said. In an accompanying commentary published in the same issue of Nature, researchers say if the findings hold up, young men may want to consider collecting and storing their sperm for later use could be what they call "a wise individual decision." Here's Dr. Lord with more on CBS This Morning:

August 23, 2012 12:09 PM

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Older fathers more likely to pass on autism-linked genetic mutations to offspring, study shows

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(Credit: istockphoto)

(CBS News) The older a new father is, the greater chances his child may develop autism, new research suggests.
Previously-held perception says older mothers are more likely to have children with autism. Though risk has been shown to increase with maternal age, some have suggested that link is overblown. Now the new study adds more clues to the ongoing mystery of what cases autism and suggests the rise in autism rates may in fact be tied to more dads deciding to wait longer to have children.
Complete Coverage: Autism Awareness
Study: Father's age a likely factor in autism
Common myths about having a child later in life
"It is of interest here that conventional wisdom has been to blame developmental disorders of children on the age of mothers, whereas the only problems that come with advancing age of mothers is a risk of Down syndrome and other rare chromosomal abnormalities," study author Dr. Kari Stefansson, CEO of deCODE Genetics, said in a press release. "It is the age of fathers that appears to be the real culprit."
Several studies have found links between autism and a greater presence of certain genetic mutations. For the new research, scientists at deCODE Genetics in Reykjavik, Iceland kicked off one of the largest genome studies ever. They examined associations between conditions like autism and schizophrenia and genetics to find out what leads to mutations.
The researchers sequenced the whole genomes of 78 Icelandic families with offspring who had been diagnosed with autism or schizophrenia, then sequenced the genomes of an additional 1,859 Icelanders from the general population to provide a comparison group. Their analysis showed every one-year increase in a father's age correlated to a two mutation-per-year increase in the child. Fathers in the study were an average age of 29.7 years old.
A father's age could account for 15 to 30 percent of cases of autism - and an increase in schizophrenia as well - the study showed. Stefannson told Nature News that a 36-year-old would pass on twice as many mutations to his child as a 20-year-old new father, and a 70-year-old would pass on eight times as many.
The findings were published August 23 online in the journal Nature.
Their scientists also reported finding offspring mutations that had previously been implicated in both conditions, in addition two identifying two new genes - CUL3 and EPHB2 - which were tied to mutations in the autism-parent group.
"Our results all point to the possibility that as a man ages, the number of hereditary mutations in his sperm increases, and the chance that a child would carry a deleterious mutation that could lead to diseases such as autism and schizophrenia increases proportionally," Stefansson said.
Dr. Cathy Lord, director of the Center for Autism and the Developing Brain at Weill Cornell Medical College and New York Presbyterian Hospital in New York City, told CBS This Morning that these is general deterioration in genes as people age. With fathers, those mutations occur more often in men's sperm and are more likely to be passed onto to their children - and maybe one of those mutations is associated with autism or schizophrenia.
Dr. Delores Maldespina, a psychiatrist at NYU Langone Medical Center, told CBS Evening News that she finds the research eye opening.
"This study shows that new mutations are frequent enough as men age that fathers aging alone can explain the increase for the risk of autism," she said. "When these diseases present without a family history, the origin is in the sperm of the man and that the risk goes up as the man ages."
The country's autism rate in March rose 25 percent to one out of 88 children (previous rate was one in 110), with some experts theorizing the rate may be due to improved diagnosis or environmental factors.
The number of men 40 and older who father a child has increased by more than 30 percent since 1980, the CBS Evening News reported.
But Yale researcher Dr. Stephan Sanders warned it's too soon to definitively say the father's age is the top factor.
"So I think it is fair to say increasing father's age does increase the instance of autism but that effect is small," Sanders said.
In an accompanying commentary published in the same issue of Nature, researchers say if the findings hold up, young men may want to consider collecting and storing their sperm for later use could be what they call "a wise individual decision."
Here's Dr. Lord with more on CBS This Morning:

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