Scientists from King's College London have identified patterns
of epigenetic changes involved in autism spectrum disorder (ASD) by
studying genetically identical twins who differ in autism
traits.
The study is the largest of its kind and 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 behaviour traits.
ASD affects approximately 1 in 100 people in the UK and involves
a spectrum of disorders which manifest themselves differently in
different people. People with ASD have varying levels of impairment
across three common areas: deficits in social interactions and
understanding, repetitive behaviour and interests, and impairments
in language and communication development.
Evidence from twin studies shows there is a strong genetic
component to ASD and previous studies suggest that genes that
direct brain development may be involved in the disorder. In
approximately 70 per cent of cases, when one identical twin has
ASD, so does the other. However, in 30 per cent of cases, identical
twins differ for ASD. Because identical twins share the same
genetic code, this suggests non-genetic, or epigenetic, factors may
be involved.
Epigenetic changes affect the expression or activity of genes
without changing the underlying DNA sequence - they are believed to
be one mechanism by which the environment can interact with the
genome. Importantly, epigenetic changes are potentially reversible
and may therefore provide targets for the development of new
therapies.
The researchers studied an epigenetic mechanism called DNA
methylation. DNA methylation acts to block the genetic sequences
that drive gene expression, silencing gene activity. They examined
DNA methylation at over 27,000 sites across the genome using
samples taken from 50 identical twin pairs (100 individuals) from
the UK Medical Research Council funded Twins Early Development
Study: 34 pairs who differed for ASD or autism related behaviour
traits, five pairs where both twins have ASD, and 11 healthy twin
pairs.
Chloe Wong, from King's College London's Institute of
Psychiatry, said: "We've identified distinctive patterns of DNA
methylation associated with both autism diagnosis and related
behaviour traits, and increasing severity of symptoms. Our findings
give us an insight into the biological mechanism mediating the
interaction between gene and environment in autism spectrum
disorder."
DNA methylation at some genetic sites was consistently altered
for all individuals with ASD, and differences at other sites were
specific to certain symptom groups. The number of DNA methylation
sites across the genome was also linked to the severity of autism
symptoms suggesting a quantitative relationship between the two.
Additionally, some of the differences in DNA methylation markers
were located in genetic regions that previous research has
associated with early brain development and
ASD.
Jonathan Mill, from King's College London's Institute of
Psychiatry and the University of Exeter, 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 study was funded by Autism Speaks, Medical Research Council
UK (MRC) and the Brain and
Behavior Research Foundation (NARSAD).
The paper, Methylomic analysis of monozygotic twins discordant for autism
spectrum disorder and related behavioural traits, is published
in Molecular Psychiatry.