Researchers have identified a new set of inherited intermediary activity genes associated with autism spectrum disorders and showing links to other behavioral disorders. They believe these findings demonstrate the need to involve 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 genetics of autism and includes genetic data from nearly 43,000 individuals. . with autism. The results show differences in genetic influences between individuals on the autism spectrum.
“Autism is a spectrum and includes profoundly autistic individuals who often have cognitive differences and/or epilepsy, as well as gifted and exceptional individuals, often in specific areas. We now understand that the genetic contributions of different phenotypes vary depending on the genes involved, when it is the activation of these genes during brain development and the reproduction 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 variations.
Autism is widely known to be inherited, but previous studies have primarily identified autism genes with de novo variants (DNVs)—variations that occur spontaneously in germ cells before pregnancy—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 sufferers’ brains from 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, the researchers analyzed 19,843 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 relevant gene.
About 70% of this genetic contribution can be attributed to genes known to be autism or neurodevelopmental disorders. However, this means that although known autism-related genes are responsible for most de novo variants, there are other genes that have yet to be identified.
The researchers then 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 without cognitive differences or autism. Among these genes, five have not yet been implicated in neurodevelopmental disorders.
Autistic individuals who carry inherited variants in these “medium-effect” genes are less likely to show cognitive differences than autistic individuals who carry LOF variants in established autism genes, such as CHD8 and SCN2A.
“Most of the parents who carried these genetic variants in our study did not have cognitive differences or autism, but we know that these genes are linked to 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.
