Autism risk for children with older fathers

Child mutations stem from paternal side, landmark study shows

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."