About one in 100 people have a form of autism spectrum disorder, or ASD. These can involve deficits in social interactions and understanding, repetitive behavior, and interests, or impairments in language and communication development. On the spectrum of ASD, symptoms manifest themselves differently in different people.
Although ASD is highly heritable, that is, passed to children in their genes, that’s not the whole story. A team from King’s College London, UK, looked at so-called “epigenetic changes” involved in ASD, in which the environment affects the expression of genes without changing the underlying DNA.
This type of change is potentially reversible with treatment. The idea that epigenetic influences may be partly responsible for the development of ASDs has gained popularity in recent years.
The team focused on DNA methylation, which blocks the genetic sequences behind gene expression, and can “silence” the activity of a gene. They used genetic information from identical twins.
Because identical twins share the same genes, the fact that ASD can occur in one twin and not the other suggests that epigenetic factors may be involved. Twins are also completely matched for genetics, age, sex, maternal influences, and common environment, and are closely matched for other environmental factors.
In samples from 50 pairs of identical twins, DNA methylation at over 27,000 genome sites was examined. Among the twins, 34 pairs had one twin with ASD and one without, five pairs had ASD in both twins, and 11 pairs had no ASD.
Results showed that at certain genetic sites, DNA methylation was consistently altered for all those with ASD. But differences at other sites were symptom-specific. Autism severity was linked to the number of DNA methylation sites across the whole genome. Interestingly, some of the DNA methylation markers were seen in areas of the genome previously linked to early brain development.
Full details are published in the journal Molecular Psychiatry.
First author Dr. Chloe Wong, said, “We’ve identified distinctive patterns of DNA methylation associated with both autism diagnosis and related behavior traits, and increasing severity of symptoms. Our findings give us an insight into the biological mechanism mediating the interaction between gene and environment in ASD.”
Co-author Jonathan Mill, Ph.D., added, “Research into the intersection between genetic and environmental influences is crucial because risky environmental conditions can sometimes be avoided or changed.
“Epigenetic changes are potentially reversible, so our next step is to embark on larger studies to see whether we can identify key epigenetic changes common to the majority of people with autism to help us develop possible therapeutic interventions.”
The researchers say their study is the largest of its kind, and conclude that it “may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behavior traits.”
Commenting on the study, Alycia Halladay, Ph.D., of the autism advocacy organization Autism Speaks, which partly funded the research, says, “This is the first large-scale study to take a whole genome approach to studying epigenetic influences in twins who are genetically identical, but have different symptoms.
“These findings open the door to future discoveries in the role of epigenetics, in addition to genetics, in the development of autism symptoms.”
Twin studies are extremely useful in this area of research. The experts say this approach is considerably more powerful in detecting epigenetic differences in a range of diseases than studies of unrelated individuals with different life histories.
Epigenetic changes could occur during the lifetime or even before birth. For example, previous research has suggested that a mother’s exposure to stress, viral or bacterial infection, diet, and the drug thalidomide can increase the risk for ASD in her children.
Following birth, many environmental factors can trigger epigenetic changes. These include nutrition, intake of specific compounds such as alcohol and nicotine, some chemicals in the living space or workplace, and some medications.
Altogether, the study adds to a growing body of research that suggests environmental and epigenetic factors play a stronger role in the development of ASD than previously thought. Epigenetic changes such as DNA methylation appear to be vital for understanding the complexity of autism genetics.
Wong, C.C.Y., Meaburn, E.L., Ronald, A., Price, T.S., Jeffries, A.R., Schalkwyk, L.C., … Mill, J. Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Molecular Psychiatry, 23 April 2013 doi: 10.1038/mp.2013.41