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Epigenetic changes shed light on biological mechanism of autism

23.04.2013
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, published in Molecular Psychiatry, 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% of cases, when one identical twin has ASD, so does the other. However, in 30% 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 (MRC) funded Twins Early Development Study (TEDS): 34 pairs who differed for ASD or autism related behaviour traits, 5 pairs where both twins have ASD, and 11 healthy twin pairs.

Dr Chloe Wong, first author of the study from King's College London's Institute of Psychiatry, says: "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.

Professor Jonathan Mill, lead author of the paper from King's College London's Institute of Psychiatry and the University of Exeter, says: "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."

Dr Alycia Halladay, Senior Director of Environmental and Clinical Sciences from Autism Speaks who 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."

The study was funded by Autism Speaks, Medical Research Council UK (MRC) and the Brain and Behavior Research Foundation (NARSAD). The twins were selected from the Twins Early Development Study (TEDS) which is funded by the MRC with additional support from the US National Institutes of Health.

Paper reference: Wong, C.C.Y et al. 'Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits' Molecular Psychiatry (2013) doi: 10.1038/mp.2013.41

For a copy of the paper or interviews with the authors, please contact Seil Collins, Press Officer, King's College London, Institute of Psychiatry. Email: seil.collins@kcl.ac.uk or tel: (+44) 0207 848 3577/(+44) 07718 697 176

About King's College London:

King's College London is one of the top 30 universities in the world (2012/13 QS international world rankings), and was The Sunday Times 'University of the Year 2010/11', and the fourth oldest in England. A research-led university based in the heart of London, King's has more than 25,000 students (of whom more than 10,000 are graduate students) from nearly 140 countries, and more than 6,500 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £525 million (year ending 31 July 2011).

King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org.

The College is in the midst of a five-year, £500 million fundraising campaign – World questions|King's answers – created to address some of the most pressing challenges facing humanity as quickly as feasible. The campaign's five priority areas are neuroscience and mental health, leadership and society, cancer, global power and children's health. More information about the campaign is available at http://www.kcl.ac.uk/kingsanswers.

Seil Collins | EurekAlert!
Further information:
http://www.kcl.ac.uk

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