First common risk genes discovered for autism

A study led by researchers from the Danish project iPSYCH and the Broad Institute in the United States revealed the first common genetic risk variants for autism and uncovered genetic differences in clinical subgroups of autism. Discovery means that we can in the future determine the genes that separate diagnostic groups, establish more accurate diagnoses and provide better guidance to the person with autism disorders.

Autism is not a new phenomenon, historical records describing individuals with symptoms that are now associated with this group of disorders. It was not until 1938 that this diagnosis was made in the first person. Since then, researchers have tried to explain the cause of autism. Many suggestions have been made, but one factor has long been established: genes play an important role.

Extensive international collaboration led by the Danish iPSYCH project and the Broad Institute, as well as by several international groups organized within the framework of the Consortium for Psychiatric Genomics, has identified the first common genetic risk variants for cancer. autism and, for the first time, to highlight genetic differences. between different types of autism.

These genes increase the risk

"When we look at autism, there is an inheritance factor of up to 80%, so the genes have a big impact overall, but despite many years of work, identify precisely the genes involved were very difficult, "says the professor. Mark Daly of Broad Institute and Institute for Molecular Medicine Finland, one of the most prominent scientists of the study.

In this study, researchers compared the genomes of 20,415 people with autism to 174,280 healthy control subjects. They reported that five genetic variants increase the risk of autism. The results were recently published in the scientific journal Nature Genetics.

"We know that there are very rare genetic variants that present a high risk of autism, but they do not explain a lot of cases, but according to our estimates, there are common variants that [cause autism] when enough of them act together. In this study, we examined the approximately 9 million frequent variants found in the genomes of the people included in our study. These are genetic variants that are common in the general population and where the contribution of each variant to the risk is very low, "says Associate Professor Jakob Grove of the University of Aarhus. Senior author of the study and is a member of the research project iPSYCH.

Genetic discoveries provide an entirely new insight into the biological processes involved in the development of autism.

"By comparing genetic risk variants to gene expression and the three-dimensional structure of the genome in the developing brain, we can show that the identified risk genes are important for brain development, and in particular for development of the cerebral cortex ", explains Professor Anders Børglum from Aarhus University, research director at iPSYCH who led the study with Dr. Daly.

The researchers also found a significant overlap between the genetic makeup of autism and that of other mental disorders, such as schizophrenia and depression, but also positive cognitive features such as the level of autopsy. instruction and IQ.

"The positive correlation with the level of education may seem paradoxical, as some people with autism have reduced cognitive function and, on average, fewer people with a diagnosis of autism eventually have a higher education. has been found in several previous studies, we can confirm that in general, this correlation between autism genes and genes predisposing to a longer education does exist, "says Jakob Grove. "However, we can show that this does not apply to all subsets of autism.We find that people with Asperger's syndrome or infantile autism possess in mean more genes beneficial for education, while this is not the case for – atypical autism or unspecified autism disorders. "

Better treatment at the horizon

Autism refers to a very mixed group with different disorders of autism. Some have very pervasive developmental disorders with mental retardation, while others may function well cognitively with normal or high IQ.

"Thanks to a new and very sensitive method we have developed, we can for the first time establish genetic differences between the different diagnostic subgroups, which indicates that larger studies in the future may identify genes separating the groups. diagnostics and enable more accurate diagnosis and guidance for people with autism disorder.We also hope that the genes we identify may provide an opportunity to develop treatment or prevention of autism. disease, which we unfortunately can not offer at the moment, "says Anders Børglum.

The scientific article entitled "Identification of Common Genetic Variants of Autism Spectrum Disorder" was published in Nature GeneticsFebruary 2019.

Provided by
University of Aarhus