Rare Variants in Genes may Raise the Risk of Autism

They identified and replicated a rare class of genetic variants that are passed (over-transmitted) from parents without autism to children with autism.

“While most autism studies focus on de novo mutations, this study focuses on rare inherited mutations, which are often understudied in autism,” says Dr. Wilfert.

“We find that these variants are individually less damaging than de novo mutations but have the potential to contribute almost as much risk and impact the same molecular pathways, through a distinct set of genes. These variants, however, are only able to persist in the general population for a few generations before being selected out by evolution.”

“It is widely understood that de novo mutations cannot and do not explain all of the genetic causes of autism, a phenomenon sometimes referred to as ‘missing heritability,’ ” says Pamela Feliciano, Ph.D., Scientific Director, SPARK (Simons Powering Autism Research).

SPARK database contributed more than 50 percent of the genetic data analyzed in this study, including exomes from 21,331 SPARK participants and 6,539 of them with autism spectrum disorder (ASD).

Search was performed on de novo changes and ultra-rare inherited variants. As more genomes come online, larger categories of variants will be accessible for analysis.

“Interestingly, the vast majority of those variants (95%) are not found in genes already known to be autism genes, indicating that there is much more to be learned about autism genetics,” says Dr. Feliciano, noting that this study is the first step in a much larger investigation.

“While the current study is not large enough to confidently identify individual genes that have these rare inherited variants, we are learning more about these genes. Future research that focuses on multiplex families is increasingly important to yield novel insights.”

This class of rare inherited variants is more prominent in families with multiple members with autism than in families with only one affected individual.

Kids with ASD in these families are more likely to carry two of these variants as compared with their unaffected siblings.

There is a need for greater diversity when conducting these kind of studies, as investigators were less able to detect rare variants in people who belong to ancestral groups that are underrepresented in genomic research, including people of African, East Asian and South Asian descent.

Source: Medindia