A novel proof-of-concept study is suggesting epigenetic biomarkers in a father's sperm can potentially predict how susceptible their offspring will be to developing autism spectrum disorder (ASD). The research is still in preliminary stages so requires further investigation in larger cohorts before it is validated as an accurate diagnostic tool.
The causes of ASD are still largely a mystery to scientists, however, it is thought to be linked to a complex combination of genetic and environmental factors. Paternal age is one well-studied risk factor, with estimates suggesting ASD risk in offspring increases by 28 percent for fathers aged between 40 and 49, and climbs to 70 percent for fathers over the age of 50.
As we age, certain genes in our body can be switched on or off through environmental and lifestyle influences. These changes to our DNA can be detected by methylation markers on certain genes. They don’t signal alterations to a person’s underlying DNA but instead point to changes in gene expression, known as epigenetic changes.
Greater volumes of epigenetic DNA methylation alterations in sperm can be detected as men age. This new research set out to explore whether patterns of epigenetic alterations in fathers' sperm correlate with autism susceptibility in their offspring.
The study, from an international team of researchers, recruited 13 men with children who have ASD and 13 men with ASD-free children. A massive genome analysis comparing sperm from the two cohorts revealed 805 specific regions of DNA methylation could distinguish the groups.
Another 18 men were then recruited for a series of blind tests to explore whether these epigenetic patterns in sperm could predict whether the men were parents of children with ASD. The sperm biomarkers correctly identified the status of the men's offspring with 90 percent accuracy. Only two of the men delivered false negative results.
Michael Skinner, corresponding author on the study from Washington State University, is cautious to not overstate what these findings imply. His team is currently working to validate these epigenetic biomarkers in a larger cohort of 100 men.
The initial outcome the research seems to be working towards is a diagnostic tool that helps parents better evaluate the risk of ASD in their offspring. This could allow doctors to monitor high-risk children from earlier stages, before the condition initially appears, or even explore ways to mitigate potential environmental triggers in those most at risk.
“We can now potentially use this to assess whether a man is going to pass autism on to his children,” notes Skinner.
Another compelling outcome from this research, should it be verified in larger cohorts of men, is it introduces a novel way to investigate exactly what general factors can contribute to ASD risk. Skinner suggests learning how these epigenetic markers were generated in the first place could help point to ways to prevent ASD.
“We found out years ago that environmental factors can alter the germline, the sperm or the egg, epigenetics,” says Skinner. “With this tool we could do larger population-based studies to see what kinds of environmental factors may induce these types with epigenetic changes.”
Needless to say, this is a preliminary study drawn from a very small cohort of men, so general conclusions should be tempered. But nevertheless, this is a compelling proof-of-concept that, with further work, could hopefully shed some light on the development of ASD.
The new study was published in the journal Clinical Epigenetics.
Source: Washington State University
