Image by Gerd Altmann from Pixabay
While scientists have identified hundreds of different genes that are associated with autism, a new Yale-led study suggests that the specific genes may be less important than the pathway they take to the brain.
May 6, 2026 - By Karen Guzman - In recent years scientists have identified hundreds of different genes associated with autism, a burst of discovery that has prompted a new and perplexing question: how can so many different genes produce the same, or very similar outcomes in the brain?
A new Yale-led study offers fresh insight, revealing how the diverse range of genes linked to neurodevelopmental disorders like autism disrupt the brain in similar ways — a finding that could ultimately open the door to new treatments.
The researchers found that these genes “converge” on a shared set of biological pathways in the brain, triggering similar downstream effects as brain cells mature.
The study, published in the journal Nature Neuroscience, was co-led by author Kristen Brennand, the Elizabeth Mears and House Jameson Professor of Psychiatry at Yale School of Medicine (YSM), and Ellen Hoffman, an associate professor in the Yale Child Study Center.
“It’s been really challenging to put our finger on what causes autism,” said Brennand. “This research gives us a new target to study: Not the genes themselves but the way they converge along the same neural pathways.”
While the genetics of autism have been studied for two decades, the level of discovery is accelerating. In 2020, one research paper alone identified 102 genes linked to autism. That number, Brennand said, is expected to jump to 250 genes as researchers increasingly gain access to enough DNA from people with autism to identify more genes linked to the disorder.
[S]everal of the drugs improved behavioral abnormalities in the fish, perhaps offering early evidence that targeting convergent pathways could have therapeutic potential.
“The question that I’ve been asking — across psychiatric disorders [generally] but around autism specifically — is, ‘Is there a subset of these autism genes that somehow have the same effect?’”
In the new study, Brennand’s team was led by associate research scientist Meilin Fernandez Garcia, PhD student Kayla Retallick-Townsley, and senior researcher Novin Balafkan.
Using a CRISPR gene-editing tool, they switched off 23 genes associated with neurodevelopmental disorders in human brain cells. They then tracked how each genetic disruption altered gene activity across different stages of brain development.
Critically, they found that many of the at-risk genes produced similar effects downstream as brain cells matured. But they first converged in the same neural pathways, including pathways involved in synaptic communication, regulation of gene expression, and mitochondrial function, which governs how cells produce energy, the team found.
This discovery is important because it points to the neural pathways as potential biological targets for future treatment. In other words, rather than developing therapies for each individual gene mutation, scientists may be able to focus on those shared pathways.
"Perhaps one day we’ll have a drug — or supplement as safe as folic acid — that can guard against neurodevelopmental disorders," said Kristen Brennand.
To further test these findings, Hoffman’s team, led by April Pruitt, a Ph.D. student in YSM’s Interdepartmental Neuroscience Program, and Elizabeth Davidson, a postdoctoral researcher, used zebrafish models engineered to carry some of the genetic mutations seen in neurodevelopmental disorders. (Zebrafish are increasingly used in autism research because they have a genetic profile that is remarkably similar to that of humans. They’re also easy to manipulate genetically and produce large numbers of offspring at a time.)
The researchers then tested drugs which are predicted to counteract the genetic disruptions in the pathways.
They found that several of the drugs improved behavioral abnormalities in the fish, perhaps offering early evidence that targeting convergent pathways could have therapeutic potential.
Overall, Brennand said, the findings support a growing view in neuroscience that the complexity of neurodevelopmental disorders may arise not from entirely distinct causes, but from different genetic routes leading to common biological endpoints.
Targeting these shared endpoints might open the door to more precise, and potentially broadly effective, treatment approaches.
“One possibility that I throw around is how we prescribe folic acid supplements to every pregnant woman to guard against neural tube defects, even though not every fetus is at risk of these defects.” Brennand said. “Perhaps one day we’ll have a drug — or supplement as safe as folic acid — that can guard against neurodevelopmental disorders.”
Does this finding mean that researchers are getting closer to understanding what causes autism?
“I like to say that we’re 20 to 30 years behind cancer research,” Brennand said. “Researchers have been finding cancer genes since the 1980s, and we’ve been finding autism genes since about 2010. But we’re getting there.”