More pieces of the autism puzzle uncovered

Ever since the first autism diagnosis was made in 1938, researchers have been trying to clarify where the disorder originates. There have been many suggestions – along with many disagreements. But one thing has been clear for a while: Genetics play a major role with a heritability of up to eighty per cent.

The largest study so far of rare genetic variants has now identified 102 new so-called risk genes for autism. The results have just been published in the international journal Cell.

"Broadly speaking, there are two types of genetic variants which play a role in autism. There are uncommon genetic variants that few people have, although these may have a big effect, and then there are frequent variants which we all carry some of, and which each contribute in a very small way to the risk," says Associate Professor Jakob Grove from Aarhus University, who is one of the driving forces behind the Danish contribution and a member of the iPSYCH research project.

Better treatment in sight 

In the study, the researchers mapped the DNA building blocks in the genes of 35,584 individuals, of whom 11,986 had autism. The researchers then determined how many times each gene is affected by variants with “protein disrupting consequences”, as the researcher puts it. "If a gene is more often hit by these mutations among people with autism than among people without it, this indicates that the gene is involved in the processes that lead to autism, and is thus designated as a risk gene," explains Jakob Grove. The majority of the identified gene-destroying mutations are new mutations that are only found in the person with autism and not in their parents. 

The genetic findings provide an entirely new insight into the biological processes that are involved in the development of autism. Some of the genes identified alter early development broadly, while others appear to be more specific to autism. Most of the genes help determine how neurones communicate with each other or they regulate the expression of other genes.

"This new knowledge could provide a better basis for understanding autism. For example, it may help us to make a diagnosis earlier, which we already know makes life easier for people with autism and their relatives. It’s also conceivable it could contribute to the development of personalised medicine for those who may want this," says Jakob Grove. In other words, the results of the study may turn out to be crucial for the treatment of psychiatric disorders in the future.

However, he also emphasises that the new findings can only explain a few cases of autism as these genetic variants are only present in few individuals. ”For this reason, iPSYCH continues to study both rare and more frequent genetic variants,” he says.

Background for the results: 

• The research has been carried out in collaboration with the Autism Sequencing Consortium (ASC) and the project is anchored at Mount Sinai in New York. In addition to researchers from Aarhus University, the Broad Institute in Boston, UCSF in San Francisco and Carnegie Mellon University in Pittsburgh have also participated along with researchers from altogether more than 50 sites.
• The research was financed by the Lundbeck Foundation, among others.
• The scientific article can be read in Cell.

Contact 

Associate Professor, Jakob Grove 
Aarhus University, Department of Biomedicine 
Tel.: (+45) 2980 1768. 
Email: grove@biomed.au.dk 

Professor and Centre Director, Anders Børglum
Aarhus University, Department of Biomedicine 
Tel.: (+45) 6020 2720 
Email: anders@biomed.au.dk