Epigenetic Biomarkers May Help Assess a Father’s Likelihood of Having an Autistic Child

Autism rates have risen steadily in the past two decades, now affecting an estimated 1 in 54 children in the US. Efforts to better understand this condition and treat it effectively have risen, too. However, the underlying causes of autism spectrum disorder (ASD) remain unclear, and there is no known preventative measure or cure.

But with research on the rise, scientists are coming closer to some answers. For one, ASD appears to be primarily related to the father’s transmission. While genetic factors have been attributed to the etiology of ASD, it is believed that epigenetic, environmental factors may play a more important role.

Recent evidence has shown that epigenetic alterations such as DNA methylation correlate with ASD. To determine more precisely how, a team of researchers from Washington State University (WSU), Valencia Clinical Research Center, and Valencia University in Spain set out to identify which paternal DNA methylation signatures are associated with ASD in offspring. The study, recently published in the journal of Clinical Epigenetics, was successful in finding specific regions in the DNA of sperm that could conceivably act as epigenetic biomarkers for autism predisposition.

Autism is a complex developmental disability of the brain that typically appears in early childhood. Recognized as a “spectrum” disorder due to its range in variation and severity, ASD is a lifelong condition that causes problems that affect a person’s social, physical, and language skills.

Although children can inherit ASD from either parent, transmission from the father is considered much higher. A main reason that has been suggested for that is paternal age. According to data cited in the study, infants born to fathers between the ages of 40 and 49 have an increased risk of 28% for developing ASD, whereas that risk rises to nearly 70% in those born to men over 50.

Advanced age has been known to cause disruptions in DNA methylation in sperm, including the specific genes that correlate with ASD. DNA methylation abnormalities in the male gamete associate with infertility as well as health disparities and predisposition for disease in their offspring. In previous articles, we have discussed how environmental factors can leave epigenetic marks on sperm DNA. Plus, we have shown how epigenetic marks carried over from a parent can impact their child’s future health.

The researchers here obtained their results by examining the molecular processes that modify gene expression, specifically DNA methylation. Comparing two groups of men of similar age, those who fathered autistic children and those that did not, they were able to identify 805 differently methylated regions (DMRs) in sperm. A mixture of methylation was observed among the DMRs, 60% had a decrease and 40% had an increase, which they noted as distinct from the expected hypermethylation in sperm for male infertility and aging.

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To test their findings, the team also conducted blind tests on 18 men to determine who did and did not have children with ASD. Remarkably, they were able to identify all the fathers correctly, minus two false positives showing a 90% accuracy rate.

“We can now potentially use this to assess whether a man is going to pass autism on to his children,” said corresponding author Prof. Michael Skinner, WSU. “It is also a major step toward identifying what factors might promote autism.”

Additional research, along with expanded clinical trials, is needed to validate the biomarkers for medical use. However, the study does provide proof of concept that such a diagnostic tool can be developed. Having this ability to test for ASD susceptibility biomarkers could potentially improve the health care provided to patients with ASD. It could also provide parents with risk assessment and possible preventative measures for reproductive/fertility care.

Skinner and his colleagues have plans to work on a larger study to include more than 100 men participants. Moreover, the author believes that the biomarkers could also be used to trace the origins of the epigenetic changes.

“We found out years ago that environmental factors can alter the germline, the sperm or the egg, epigenetics,” Skinner added. “With this tool, we could do larger population-based studies to see what kinds of environmental factors may induce these types with epigenetic changes.”

Source: Garrido, N., et al. Sperm DNA methylation epimutation biomarker for paternal offspring autism susceptibility. Clinical Epigenetics. 2021; 13(1)

Reference: Sara Zaske. Biomarkers in fathers’ sperm linked to offspring autism. Washington State University, January 11, 2021.

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