The causes of autism have been both a point of confusion and contention for some time now. Could autism spectrum disorder (ASD) be rooted in genetics, or can we attribute environmental factors to its development? Researchers at Cold Spring Harbor Laboratory (CSHL) believe they are getting closer to the answer. Working off the theory that roughly half of autism cases are caused by a chance combination of genetic mutations, their new study published in the journal Proceedings of the National Academy of Sciences has found more evidence for the genetics argument.

For their study, the researchers looked at how “de novo likely gene-disruptive mutations (LGDs)” — mutations that develop at the beginning of a child’s life — occurred in genes deemed “vulnerable” and how they played a role in ASD development. They also looked at whether these gene-disruptions transferred between generations.

During his research, CSHL assistant professor and quantitative biologist Ivan Iossifov found mutated genes that sometimes contribute to the development of ASD actually have less mutations than most other human genes. This runs contrary to the idea that more genetic mutations lead to worse health. But why exactly would LGDs have fewer genetic mutations than other genes?

Iossifov explained that when these genetic mutations occur in a child, and give way to ASD, they often do not get passed on to another generation. According to Iossifov’s research, many diagnosed with severe autism will not reproduce, and therefore their genetic material is less likely to evolve and mutate.

With this information in mind, researchers were better able to understand which genes with LGDs could be categorized as “autism genes.” Starting with 500 likely genes, researchers were able to narrow down the list to 200 of the most likely genes related to autism.

In addition to discovering which genes were likely involved, the researchers also looked into how parents could potentially carry these LGDs and pass them on to their children without their health being affected. For the study, researchers looked at families through the Simons Simplex Collection (SSC) database. They found that in families with autistic children, parents could be carriers of the LGD mutations, and that these mutations were seen more frequently in their children with ASD rather than their children without the disorder. Along with this, they also found that mothers were most likely to carry the genetic mutations.This finding gives further credence to the theory that LGDs play a role in autism.

Not only do the results give further credence to the theory that LGDs play a role in autism, but the researchers believe their findings also support a 2007 study published by CSHL Professor Michael Wiglerand and Dr. Kenny Ye, a statistician at Albert Einstein College of Medicine. In their study, the two researchers predicted mothers, though unaffected by the LGDs, could be carriers and later transmit it to their children. This belief stems from the fact women have an unexplained factor that protects them more frequently from these mutations that often cause ASD in males — it is well-known that four times as many men are diagnosed with autism than women.

The researchers also note that although their findings lend further support to established theories of ASD’s link to disruptive genetic mutations, more research must be done to further understand this connection.

Source: Iossifov I, Levy D, Allen J, et al. Low load for disruptive mutations in autism genes and their biased transmission. PNAS. 2015.