Father's age seen as crucial to baby's disease risk

Newborn baby girl right after delivery, shallow focus

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 said on Wednesday.

In a study which turns conventional thinking on its head, researchers 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."

He said this age-linked increase in mutations proportionally increased the chance a child might carry a harmful mutation that could lead to conditions like autism and schizophrenia.

"It is the age of fathers that appears to be the real culprit," he added.

The study found an average of two more new gene mutations appeared in offspring for every year of increase in a father's age - meaning 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 since there are so many other factors involved in the health of offspring.

Women who conceive later in life are at higher risk of having babies with Down syndrome and other rare chromosomal abnormalities, but 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 its results suggested men should recognize there is a price to pay for remaining fertile into old age.

"Price is paid by children"

"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," 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.

Autism spectrum disorders can range from severe mental retardation with a profound inability to communicate, to relatively mild symptoms combined with some high levels of function such as those seen in people with Asperger's syndrome.

Among core features of the disorders are poor communication skills and difficulties with social engagement. In the United States, an estimated 1 in 88 children have autism, while in Europe the rate is thought to be around 1 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 previously have found dozens of genes that may raise the risk of autism. But genetic causes only explain about 10 percent 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.

Other studies in Iceland have shown that the risk of both schizophrenia and autism increases significantly with a father's age at conception, and that men are having children later. The average age of Iceland fathers conceiving in 2011 was 33 years, up from 27.9 years in 1980.

Stefansson stressed that demographic changes of this type - such as men tending to have children later - are not unique to Iceland, so suggest the reported increase in autism rates around the world was at least partially due to older fathers.