A new study supported by OHSU researchers has identified a group of genes that contribute to autism primarily through inherited variants, allowing for a better understanding of a broader range of conditions across the autism spectrum.
The findings, published this month in Nature Genetics, advance knowledge of the complex genetics of autism. Researchers used data from the SPARK (Simons Powering Autism Research) research cohort, which includes genetic data from nearly 43,000 people with autism — the largest cohort to date.
"Expanding our understanding of the genetic influences of autism is crucial, and we're now beginning to look at things from a gene-first perspective, as opposed to only considering behavioral components," said Brian O'Roak, Ph.D., associate professor of molecular and medical genetics in the OHSU School of Medicine, whose team supported data analysis efforts for the study. "If we can identify on a cellular level how these risk genes operate and alter development, we can learn how brains work differently and provide better treatment and support for individuals on the spectrum."
Although it is generally known that autism has a strong genetic risk, previous studies have mostly identified autism risk genes disrupted by sporadic mutations, known as de novo variants. These types of genetic variants have profound effects on the brain, but only 20% to 30% of individuals with autism have them, leaving a large gap in knowledge about other genetic factors associated with autism. Until now, research studies were too small to be able to systematically detect moderate-risk genes, which often include risk from inherited variants that run in families. The discoveries made in this study can begin to explain conditions all across the autism spectrum.
The research team analyzed 19,843 participants with autism, along with one or both of their biological parents. After establishing a first set of candidate risk genes, they tested these genes in another 22,764 individuals with autism and 236,000 people without autism from other studies. After conducting a meta-analysis, they identified 60 highly significant autism risk genes, five of which are newly associated with autism.
Understanding these genetic influences can help identify different sub-types of autism, which can present with similar history, development patterns and behavioral conditions. Furthering research in this area can improve tracking of these sub-types and help to create a network of people in the autism community who can share resources and provide support, O'Roak said.
OHSU was a part of a team of institutions involved with this research including Simons Foundation, Columbia University Medical Center, University of Washington, University of Iowa Carver College of Medicine, David Geffen School of Medicine UCLA, Washington University St. Louis and the SPARK Consortium.
While these findings provide groundbreaking information on the genetics of autism, O'Roak noted that researchers still have much to learn. The findings allow researchers to say with confidence that specific genetic variants increase the risk of developing autism; however, genes with more moderate risk may have disruptions to biology that are less severe, which makes identifying and understanding those more difficult. Research must continue to identify a complete set of autism risk factors that represent all the possible sub-types of autism, in order to provide the best clinical knowledge and treatment options to individuals with autism, no matter where they are on the spectrum.
The SPARK initiative is funded by the Simons Foundation as part of SFARI. This research was supported by grants from the National Institute of Mental Health, National Institutes of Health and the Simons Foundation.
