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Beyond Autism Genes: Epigenetic Differences in Identical Twins

By studying identical twins who differ in autism traits, researchers find evidence of environmental influences on gene expression
April 23, 2013


A “Top Ten Advances in Autism Research 2013” Selection
See all the year’s “Top Ten” here.



Researchers studying identical twins who differ in autism traits have identified what may be a major mechanism by which environmental influences contribute to – or protect against – autism. They did so by documenting tell-tale patterns in a biological system that controls gene activity without altering the genes themselves.

The report appears online today in Molecular Psychiatry. It was supported by a research grant from Autism Speaks.

This research represents the first large study to directly examine the role of epigenetics in the development of autism, says senior author Jonathan Mill, Ph.D., of King’s College London and the University of Exeter. Epigenetics refers to biological systems that control the expression, or activity, of genes without changing their underlying DNA code. It is a relatively new but rapidly advancing field of research.

Specifically, the researchers looked at DNA methylation, a mechanism that keeps genes locked in the off position. Using advanced technology, they compared areas of DNA methylation across the genomes (entire DNA sequence) of 100 identical twins (50 pairs). In some cases, both twins had autism. In others, just one or neither was affected.

“We identified distinctive patterns of DNA methylation associated with autism diagnosis, related behavior traits and increasing severity of symptoms,” says lead author Chloe Wong, Ph.D., also of King’s College London.

The researchers also note that some of the distinctive differences appeared in regions of the genome associated with early brain development.

Beyond Autism Genetics

Over the last 20 years, research has shown that autism stems, in large part, from DNA changes, or mutations, in genes involved in brain development. Much of this evidence comes from studying twins – especially identical twins, who share the same genome – or complete set of genes. When one identical twin has autism, so does the other around 70 percent of the time.

“That nearly a third of identical twins differ in autism symptoms makes clear that there are also nongenetic influences at play in some cases,” Dr. Wong comments. Though they share the same womb, identical twins can experience different stresses during pregnancy and birth, she notes. Along these lines, studies have associated increased autism risk with certain birth complications. Exposure to certain chemicals during pregnancy or early infancy may also affect autism risk.

Still, the question remained, how do such nongenetic influences influence the development of autism? In recent years, research has suggested that they may do so through epigenetics. That is, by affecting the systems that turn genes on and off at the proper time and place. (More on environmental epigenetics and autism here.)

Outside of the field of autism, a number of studies have shown that influences such as prenatal stress and exposure to certain pollutants produce epigenetic changes that can interfere with normal gene function.

A Landmark Study

“This is the first study to take a whole genome approach to studying epigenetic influences in twins who are genetically identical but have different symptoms,” comments Alycia Halladay, Ph.D., Autism Speaks senior director of environmental and clinical sciences. “These findings open the door to future discoveries in the role of epigenetics – in addition to genetics – in the development of autism symptoms.”

The study was the largest-ever of its kind. However, larger studies enrolling more individuals are needed to confirm the findings and explore their implications.

Research into the intersection between genetic and environmental influences is crucial, Dr. Mill concludes. “Sometimes risky environmental conditions can be avoided or even changed,” he notes. Potentially, advances in understanding autism epigenetics might also advance the development of tailored treatments.

In addition to funding by Autism Speaks, the study received support from the UK Medical Research Council. The twins were from the Twins Early Development Study, which is funded by the Medical Research Council and the US National Institutes of Health.