Carnegie Mellon University
February 11, 2020

Largest Genetic Study Points to Autism Culprits

A multi-institutional study identified more than 50 new gene variants that are closely linked to symptoms associated with autism spectrum disorder.

By Stacy Kish

Stacy Kish
  • Dietrich College of Humanities and Social Sciences
  • 412-268-9309

Affecting one in 59 children in the United States, autism spectrum disorder (ASD) is characterized by repetitive behaviors, nonverbal communication and challenges with social situations. Many studies have explored different genetics factors that influence the severity of the disease. A recent study brought together the largest genetic dataset to identify an additional 53 genes directly linked with symptoms of the disorder. The work opens new pathways to explore during the diagnosis and treatment of ASD.

The results of the multi-institutional study were published online in the journal Cell.

The landmark study explored the genetic make-up of more than 35,000 people, of which almost 12,000 participants managed different levels of ASD severity. In the study, the researchers identified variations in 102 genes. Almost half of the genes are new to the scientific community and 53 are more specific to ASD compared to other intellectual disability or developmental delay.

“A long list of genes doesn’t immediately lead to ideas for therapy or treatment of ASD, but it is the first step toward such breakthroughs,” said Kathryn Roeder, UPMC Professor of Statistics and Life Sciences at CMU and co-senior author on the paper. “With this rich list of genes, we expect to make progress discovering when, where and how malfunctioning of these genes can lead to autism.”

Previous studies pointed to the importance of rare variants in the risk of ASD.  The research team focused on identifying rare inherited variants that arise from new genetic alterations to better understand the genetic factors at play in the development of ASD.

In order to identify these rare variants, the team needed a large dataset. They turned to the Autism Sequencing Consortium to obtain the genetic samples from thousands of people from around the world. Many of the samples came from patients with ASD and family members without the disorder, providing more than 21,000 family-based samples.

The gene variants identified fell into one of two buckets. One group played a role in the neural connections in the brain. The other group played a role in switching on and off genes that affect brain development. Both groups are commonly expressed in the cortex, the outer layer of the brain. The variants occur in both excitatory neurons that facilitate neural activity as well as inhibitory neurons that deter activity. According to Roeder, these results support the idea that there are many roads that lead to ASD symptoms.

“This project was inspiring to me because dozens of researchers from all over the world chose to pool their resources to ensure that we had enough data to yield discoveries,” said Roeder. “In essence, scientists bypassed the opportunity to have a paper of their own so that we could achieve a better results for the community.” 

Roeder was joined by colleagues at multiple institutions in the project, titled “Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism,” in the journal Cell. The researchers received funding from the Autism Science Foundation, National Human Genome Research Institute, National Institute of Mental Health, the National Science Foundation and the Simons Foundation.