Epigenetic link to autism

US scientists have identified a genetic trait that is strongly associated with autism. The genetic change does not involve a mutation within the DNA sequence of a gene but instead involves an alteration in the physical structure of the DNA which affects the way a gene is turned on and off. The researchers hope that the new findings will lead to novel ways to diagnose and treat autism.

In the body, the activity of specific genes is partly regulated by small molecules, called methyl groups, that are attached to the areas of the genome that control the switching on and off of each gene. The research team, from the Duke University Medical Center, North Carolina, USA, found that individuals with autism have a higher than usual number of methyl groups attached to the area of their genome that regulates a gene called the oxytocin receptor (OXTR). OXTR binds the hormone oxytocin and mediates its effects. The higher methylation status of OXTR in individuals with autism likely results in lower levels OXTR in these individuals' brains, thus making them less susceptible to the affects of oxytocin.

The oxytocin hormone is involved in social interactions, in particular, in establishing levels of trust and in the ability to read social cues. It has been used in the past to help alleviate the symptoms of autism. Dr Simon Gregory, the lead author of the study, said: 'These results provide a possible explanation of why social isolation forms part of the autism spectrum - because an autistic individual's ability to respond to oxytocin may be limited'.

The study, reported in the journal BMC Medicine, examined the methylation status of DNA from 119 individuals with autism and 54 individuals without the condition. Dr Gregory summarised: 'In both blood samples and brain tissue, the methylation status of... the oxytocin receptor gene is significantly higher in someone with autism, about 70 per cent, compared to the control population, where it is about 40 per cent.' These findings indicate that testing the methylation status of an individual's OXTR gene may prove useful in the diagnosis of autism in conjunction with other clinical tests, and may also help to identify which individuals will respond well to treatment with oxytocin. Furthermore, drugs that alter DNA methylation could potentially be used in the treatment of autism.

DNA methylation is an epigenetic trait - that is, an inherited characteristic that is not encoded in DNA gene sequences and affects gene regulation. Dr Jessica Connelly, another member of the research team, said: '[this] epigenetic link to autism is extremely exciting as it provides another opportunity for us to explore the heritability of this disorder and argues the importance of exploring epigenetic markers in complex disease.'

Epigenetics will be addressed before a mixed lay and specialist audience for the first time on Wednesday 18 November 2009 at Does Genetics Matter? Help, the annual conference of the charity that publishes BioNews, the Progress Educational Trust (PET).