IT HAS been hailed as a breakthrough that could help millions: scientists are homing in on the genetics behind autism and how genes involved in early brain wiring could hold clues as to how the disorder arises, writes CLAIRE O'CONNELL
By trawling through DNA information from large cohorts of volunteers, scientists identified variations associated with increased risk of developing autistic spectrum disorders, and found that many risk variants cropped up around genes involved in forming connections between brain cells during development. The major new studies were published online last week in the journal Nature.
But what do the findings mean in the bigger picture? Experts here have welcomed the developments, but insist they are just another step in the process of solving a complex riddle.
A child with a disorder on the autistic spectrum may have a narrow range of interests, carry out repetitive activities and find it difficult to communicate and form social relationships. Such disorders are thought to occur in 1 per cent of children and are four times more commonly seen in boys than in girls, according to the Irish Society for Autism.
“[Autism] is a disorder of development, it occurs in children who are very young and it is thought to represent disorder of neurodevelopment, so something goes wrong in how the brain develops. The result is autism or one of the autism-related disorders,” explains Michael Gill, professor of psychiatry at Trinity College Dublin, who researches the genetics of autism, schizophrenia and attention deficit hyperactivity disorder.
There have long been clues that autism has a genetic component, says Gill.
“We know it tends to a certain extent run in families but not in a clean, clear-cut pattern,” he explains. “And both twin and adoption studies would support quite a strong genetic component.”
But less sure is the number of genetic risk variants and their effects. “What we don’t know is how many genes are involved and the impact that each gene has,” says Gill, who describes two suggested models for increased risk.
“One is that common DNA variants increase risk each a very tiny amount, to autism, and there could be up to hundreds of those,” he says. “Another model is that there are many forms of autism, each of which can be substantially caused perhaps by a single genetic event or mutation, but that each mutation is extremely rare and causes only one or maybe a handful of cases.”
The latest research – which forms part of ongoing studies – indicates the reality could be a combination of the two.
By comparing DNA collected from more than 10,000 people, many of whom have an autistic spectrum disorder, US researchers found that tiny changes in the DNA around two “cadherin” genes, which are involved in brain cell connectivity, are associated with a very small increase in risk of having autism.
Meanwhile, a companion study, also published in Nature, found that larger but much rarer "copy number variation" changes in DNA also conferred an increased risk of developing autism. Here too the changes cropped up around genes involved in cell-to-cell connection, which Gill sees as an insight into the biology of how the disorders arise in early brain development.
“It’s about abnormal connectivity. It’s like an electrical circuit – if you have too many wires hanging around, you could have a real problem, or if you have too few wires and the connections aren’t good, you can have a problem too,” he explains.
“Also the brain usually makes very many more connections than it needs to as it develops and then it prunes back, and there could be a problem with this pruning process.”
Trinity and University College Dublin are currently analysing another cohort of DNA samples in a separate study – the international Autism Genome Project – which includes genetic material from about 200 volunteers in Ireland, says Gill.
He describes the emerging findings in that project as “interesting” but he is careful not to predict how the results of such genome-association studies may affect prevention, diagnosis or treatment of autistic spectrum disorders.
“It’s very exciting for the field as a whole and it is telling us more about what causes autism. It is an entry into the biology, but this is just the start, and what it means is speculation after that,” he says.
“It raises the possibilities of improvements in those areas but it doesn’t necessarily indicate any immediate likely changes to the way we make diagnoses. I would doubt that it would have any immediate relevance or importance in a clinical sense, but we just don’t know.”
However, the current findings are important in the context of the “evolving picture” of how we understand autism, notes Gill.
“If you think of it like a jigsaw puzzle, we thought initially that our puzzle might have had 100 pieces but it turned out that we probably have several thousand pieces and, yes, it is more complicated.
“But now we have identified several key pieces of that jigsaw, like corner pieces or edge pieces. And with any jigsaw, once you identify certain key pieces, other pieces start to fall into place easier,” he says.
“So the importance of this research is that it has identified key pieces of the jigsaw which will enable others to more easily identify additional pieces of the puzzle.”
The research is a move in the right direction, agrees Tara Matthews from the Irish Society for Autism. “It’s a positive move forward, it’s another step on a long road,” she says. “It’s something that may lead us at some point to prevention and better diagnosis, but that’s a long way away.”