A father’s age, not a mother’s, when a baby is conceived is the single largest factor in the risk of passing on new gene mutations to children, and may help explain why childhood autism rates are rising, scientists have said.
In a study which turns conventional thinking onto its head, researchers have sequenced the genomes of 78 Icelandic families with children diagnosed with autism or schizophrenia and found a father’s age was crucial to the genetic risk of such disorders.
“Conventional wisdom has been to blame developmental disorders of children on the age of mothers,” said Kari Stefansson, chief executive of the private firm deCODE Genetics in Reykjavik, whose work was published in the journal Nature.
“(But) our results all point to the possibility that as a man ages, the number of hereditary mutations in his sperm increases.
“It is the age of fathers that appears to be the real culprit.”
The study found that an average of two more new gene mutations appeared in offspring for every year of increase in a father’s age – meaning that the number of new mutations passed on by fathers would double every 16.5 years from puberty onwards.
However, it was not possible to say at what age this could become a concern for a man because there are so many other factors involved in the health of offspring.
Women who conceive later in life are at a higher risk of having babies with Down’s syndrome and other rare chromosomal abnormalities, but Dr Stefansson said his study showed men transmitted far more new gene mutations to children than women.
Richard Sharpe, a professor at the University of Edinburgh’s Centre for Reproductive Health who was not involved in this research, said results suggested men should recognise there is a price to pay for remaining fertile into old age.
“The price is paid by their child-ren because the older your father at conception the greater the number of gene mutations you inherit from him,” he said. “In contrast, gene mutations inherited from your mother are unaffected by her age at conception.”
The finding chimes with the results of three American studies published in April which found that spontaneous mutations could occur in a parent’s egg or sperm cells that raised the risk of autism, and that fathers were four times more likely than mothers to pass these mutations on.
Among core features of autism are poor communication skills and difficulties with social engagement. In the US, an estimated one in 88 children have autism, while in Europe the rate is thought to be around one in 100.
Diagnosis rates have been rising around the world in the past few decades and scientists have been trying to figure out why. At least part of the increase is believed to be due to better diagnosis and wider recognition of the disorders.
Scientists have previously found dozens of genes that may raise the risk of autism. But genetic causes explain only about 10 per cent of cases, and recent studies have pointed to environmental factors, possibly arising at conception, as a potential trigger.
Darren Griffin, a professor of genetics at the University of Kent who was not involved in the new study, said the age finding was significant “but not one necessarily to cause great worry among prospective older fathers”.
“There are three billion of letters in the DNA code of humans and the numbers of mutations detected in this study are in the dozens,” he said.
The average age of Iceland fathers conceiving in 2011 was 33 years, up from 27.9 years in 1980.
Dr Stefansson stressed that demographic changes of this type – such as men tending to have children later – are not unique to Iceland, so the reported increase in autism around the world was at least partially due to older fathers.