According to a new study children of older fathers have genetic changes associated with autism and other brain disorders. As of now this is seen only in lab mice. Professor John McGrath of the Queensland University’s Brain Institute and colleagues report their findings today in the journal Translational Psychiatry.
Professor McGrath said, “There's quite convincing evidence now that the offspring of older dads have an increased risk of a range of brain disorders like autism and schizophrenia and maybe even slightly lower IQ…Compared to men in their early 20s, the offspring of men over age 50 have a two-fold risk of getting schizophrenia or autism.”
Such findings come from previous epidemiological studies by McGrath and others. Now, McGrath and colleagues have used a mouse model to look at the genetics that explains this phenomenon.
Professor McGrath noted that when a boy hits puberty his sperm cells divide every 16 days, and that more divisions translate to more genetic alterations. McGrath said, “By the time a man is 40, his sperm cells have undergone 660 cell divisions, and 800 cell divisions by age 50.”
They have been looking for specific mutations called copy number variants or CNVs, in which whole “chapters” of genetic material are either deleted or repeated. Researchers believe DNA from the sperm cells of older dads are more likely to develop CNVs than that from younger dads.
McGrath and colleagues looked at the DNA of offspring from older and younger male mice, mated with mothers of the same age, and tested for CNVs that only occurred in the offspring. “We found more of these mutations in the offspring of older dads,” said McGrath. He explained that these offspring also have a different shaped brain and different behavior to those from younger fathers.
McGrath said the CNVs discovered have already been linked to brain disorders in humans. “In fact one of the mutations we found was in a well known autism gene,” he said. “That's what you call a 'lucky strike',” he said explaining that the next step is to look for CNVs in humans, but this will require expensive high throughput technology.
“As the studies are done in the next three to five years ... we predict that the offspring of older dads will have more of these CNVs,” he said. He said showing this would give insight into a potentially modifiable risk factor for autism and schizophrenia.
According to Professor McGrath, it's too early to make public health recommendations, but people should be aware that older fathers can put their youngsters at increased risk of the debilitating mental disorders. “Just as women are now aware that there are risks involved in delaying motherhood, then there may well be the need in the future for public health messages to men that there are risks involved in delaying parenthood,” he said. “It's also important because these mutations may be inherited by future generations,” he said.
Newcastle University molecular biologist Murray Cairns, with the Schizophrenia Research Institute in Sydney, said, “We've known that paternal age is a risk factor for schizophrenia and autisms and now this is a validation that it could have something to do with CNVs.”
The Malaysian Mental Health Survey(MMHS) showed that kids born to fathers 19-years-old or younger had just a 9% chance of developing a mental disorder. That number jumps to 24% when the father is at least 11-years older than the mother. The MMHS found that when the father was over 50 and 11-years-older than the mother, the rate of mental illness was 42%.
In a study published in November by Christina Hultman, an epidemiologist at the Karolinska Institute in Stockholm, research showed that the risk for mental illness spiked for father’s over the age of 40. Men between 40 and 49 were 1.4 times more likely to have children autism than men between the ages of 15 and 29. The risk increased for men above the age of 50, and at 54, men were 4.4 times more likely to have a child with autism.
Environmental stressors linked to fetal brain development challenges