A new study supports the theory that the soaring rate of autism diagnoses over recent years is partly attributable to the increasing average age of fathers.
The researchers suggests that this theory may account for as many as 20 to 30 percent of cases of autism and schizophrenia.
The risk is increased in older men because of random mutations that become more numerous with age, say scientists. The study is the first to measure the effects as they build each year.
A mother’s age, on the other hand, had no effect on the risk for these two disorders.
Experts said the findings are no reason to forgo becoming a father in later years, but they may have some influence on reproductive decisions.
The overall risk to a man in his 40s or older is around 2 percent, at most, and there are other unknown contributing biological factors.
The research opposes the common theory that the mother’s age is the most important factor in the odds of a child having developmental problems. The risk of chromosomal abnormalities, such as Down syndrome, increases with the mother’s age.
However, when it comes to certain complex developmental and psychiatric problems, the highest genetic risk begins in the sperm, not the egg, the researchers found.
Prior studies have strongly suggested this as well, including an analysis published in April that showed that this risk was higher at age 35 than 25 and slowly escalated with age. For the first time, this new study calculates how much it accumulates each year.
The scientists discovered that the average child of a 20-year-old father had 25 random mutations that could be traced to the father’s genetics. That number rose steadily by two mutations a year, reaching 65 mutations for offspring of 40-year-old men.
From the mother’s side, the average number of mutations was 15, regardless of age, the study found.
“This study provides some of the first solid scientific evidence for a true increase in the condition (of autism),” said Dr. Fred R. Volkmar, director of the Child Study Center at the Yale School of Medicine, who was not involved in the research. “It is extremely well done and the sample meticulously characterized.”
The study, led by the Icelandic firm Decode Genetics, analyzed genetic material taken from blood samples of 78 parent-child trios.
It focused on families in which parents, who had no mental disorders, had a child who developed autism or schizophrenia. This method allowed researchers to isolate brand-new mutations (de novo mutations) in the genes of the child that were not found in the parents.
Most people have these de novo mutations, which appear spontaneously at or near conception, and most are harmless. But studies suggest that there are several such changes that can dramatically increase the risk for autism and possibly schizophrenia — and the more a child has, the more likely he or she is to develop a severe disorder.
“It is absolutely stunning that the father’s age accounted for all this added risk, given the possibility of environmental factors and the diversity of the population,” said Dr. Kari Stefansson, the chief executive of Decode and the study’s senior author. “And it’s stunning that so little is contributed by the age of the mother.”
A father’s age, by itself, certainly does not explain the overall increase in diagnoses. The birthrate of fathers age 40 and older has increased by more than 30 percent since 1980, but the diagnosis rate has jumped tenfold, to 1 in 88 eight-year-olds.
And it is not clear whether the rate of schizophrenia has increased at all in that time.
Overall, these kinds of mutations may account for 20 to 30 percent of cases of autism, and perhaps schizophrenia, some experts said. The rest are probably a result of inherited genetic predisposition and environmental factors that are still the focus of various studies.
“You are going to have guys who look at this and say, ‘Oh no, you mean I have to have all my kids when I’m 20 and stupid?’ ” said Evan E. Eichler, a professor of genome sciences at the University of Washington in Seattle.
“Well, of course not. You have to understand that the vast majority of these mutations have no consequences, and that there are tons of guys in their 50s who have healthy children.”