Discovery of new genes linked to the ‘moderate effect’ of the autism spectrum

PARIS, August 29 (Benin News) –

Researchers have identified a new set of inherited intermediate-activity genes that are associated with autism spectrum disorders and show links with other behavioral disorders. They believe these findings illustrate the need to engage a wide range of research participants across the spectrum to identify the full spectrum of autism genes.

In a series of papers published in the journal Nature Genetics, researchers used data from the Simons Powering Autism Research (SPARK) research group, which was created to advance our understanding of the complex genes of autism and includes genetic data from nearly 43,000 people. with autism. The results show differences in genetic influences between people on the autism spectrum.

“Autism is a spectrum, and includes profoundly autistic people who often have cognitive differences and/or epilepsy, as well as gifted and exceptional people, often in specific areas. We now understand that the genetic contributions of different phenotypes vary depending on the genes involved, when they are Activation of these genes during brain development, and the replication of certain genetic variants in the population,” explains Spark Principal Investigator Wendy Chung, PhD.

In one study, researchers analyzed the DNA of nearly 43,000 people with autism, including 35,000 participants in the Spark Autism Study, as part of Spark’s ongoing effort to understand the comprehensive spectrum review of autism genetics. This autism cluster, the largest ever, allowed researchers to identify a group of new “medium-effect” genes that tend to contribute to autism through inherited variants.

Autism is widely known to be hereditary, but previous studies primarily identified autism genes with de novo variants (DNV) – variants that occur spontaneously in pre-pregnancy germ cells – that are not inherited. Most of these variants are also implicated in other neurodevelopmental disorders (NDDs).

Most of these genetic variants associated with autism have profound effects on the brains of sufferers at their onset. However, only 20% of people with autism have this type of genetic variant.

“We’ve known for many years from twin studies that there must be inherited genetic variants that lead to autism, but we haven’t been able to systematically identify individual genes until now,” says lead author Pamela Feliciano, Spark’s chief scientific officer. We have now identified a group of genes associated with autism, which may include inherited variants, that begin to explain a different part of the autism spectrum.

To better understand the full spectrum of autism genes, researchers analyzed 19843 participants with autism, as well as one or both of their biological parents. They found that about 20% of people with autism had de novo genetic variants that affect the function of the associated gene.

Approximately 70% of this genetic contribution can be attributed to genes known to be autism or neurodevelopmental disorders. However, this means that although the known genes associated with autism are responsible for most de novo variants, there are other genes that have yet to be identified.

Then the researchers added 22,764 people with autism and 236,000 without autism from the general population. In this meta-analysis, they identified 60 autism genes whose contribution to autism is largely due to rare inherited loss-of-function (LOF) variants inherited from parents who do not show cognitive differences or autism. Among these genes, five have not yet been implicated in neurodevelopmental disorders.

Autistic people who carry inherited variants in these “medium-effect” genes are less likely to show cognitive differences than people with autism who carry LOF variants in well-established autism genes, such as CHD8 and SCN2A.

“Most of the parents who passed on these genetic variants in our study had no cognitive differences or autism, but we know that these genes are associated with autism because we found that these variants are often inherited by children with autism,” he explains. .

“Our hypothesis is that people with autism who have these inherited genetic variants are not as likely to experience seizures and cognitive differences as people with de novo genetic variants. So far, our data strongly support this hypothesis,” concludes Dr. Feliciano.