A global study by the Autism Genome Project (AGP) involving 50 institutions worldwide including Trinity College Dublin (TCD) and University College Dublin (UCD) has contributed to a greater understanding of the genetic origins of autism.
Autism is a complex neurobiological disorder that inhibits a person’s ability to communicate and develop social relationships. It is often accompanied by behavioural challenges and is associated with disability throughout the lifespan. International prevalence rates are around 1pc for all types of autistic spectrum disorders, from severe to mild.
The results of the first phases of the AGP study were published by leading scientific journal Nature last week, and have been welcomed across the globe, with reports of the findings being published in The Guardian, The Sydney Morning Herald, New Scientist and the Los Angeles Times, among others.
The international response was welcomed by co-lead investigator Prof Michael Gill of TCD’s Department of Psychiatry in the School of Medicine, who sees it as a tribute to the high quality of the work produced by the 10-year collaboration between TCD and UCD. Gill worked alongside fellow Irish co-lead investigators Dr Louise Gallagher from TCD’s Department of Psychiatry, and Prof Andrew Green and Dr Sean Ennis from the UCD School of Medicine and Medical Science.
Genetic components of autism
“What we’ve found are some new pieces in a rather large jigsaw puzzle. Some of the pieces are already in place from work over the last numbers of years, and what we’ve done by putting in additional pieces is we’ve begun to have a vague idea of what the picture is in terms of autism genetics – autism has a large genetic component.
“The picture that is emerging is one of brain development, particularly the machinery involved around the communication between nerve cells: the mechanisms that control nerve cell growth during development; and the number of connections and the quality of the connections that the nerve cells make,” explains Gill.
The AGP reported that individuals with autism have submicroscopic sections of DNA that occur more often (duplications) or less often (deletions), called copy number variants, in their genome. The Autism Genome Project study also identified new autism susceptibility genes, including SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53–PTCHD1 locus.
“We were able to look at the data in relation to genes that are known to play a role in learning disability in general. Autism is in a sense a form of learning disability and up to 60pc of children with autism have a learning disability, as well, which is a complicating part of the disorder.
“If we are going to learn to treat and manage autism and enable people with the condition to live as normal a life as possible, then were are going to have to find out what goes wrong, how it works,” Gill says.
Funding for the APG
The APG received US$16m in funding, with the Irish contribution being a sizable US$6m. The Irish funding came via the Health Research Board and originated in the Department of Health and Children. “Irish participation involved putting the technology in place, and then producing the genetic data and putting in place funding for analytical posts, the statistical expertise to help with analysing the data, and funding on ongoing family collection. Both UCD and TCD would have employed a number of young scientists involved in this study and that grows their expertise.
“We’ve also have tremendous support from the community of families who have autism cases and autistic children throughout Ireland. One hundred and fifty Irish families have contributed to this; there were over 1,000 families involved in the study as a whole. We’ve produced over half of the data in Ireland,” says Gill.
More work to be done
“This is only essentially the first half of the data, we’ve more work to do,” Gill explains. “The rest of the data is being analysed at present. These are enormously complex data sets – there is a huge number of genetic measures taken because you’re looking at all the chromosomes across the whole genome, so that’s almost a million data points across the genome, and multiply that by 1,000 people.
“There are sequencing studies under way across the world, including by members of this consortium, and we in TCD are sequencing to try to extend the finding using that very new technology. These are cutting-edge technological developments that require both the equipment and the ability to run that equipment – it’s part of the knowledge economy that we’ve been talking about.
“This study, while not commercially orientated, could have commercial potential further down the line. It just shows you what can happen when Irish scientists collaborate – we can contribute significantly on the world stage. Investment so far in Irish science has been very effective,” says Gill.
By Deirdre Nolan