The largest study on autism to date has identified 102 genes associated with ASD.
The causes of autism are unknown. The spectrum is wide, and has varying symptoms. Because of this, scientists have theorized for some time now that there are multiple potential triggers for the disorder — some could be genetic, others environmental.
Current screening methods include behavioral observations and ticking off boxes for developmental milestones; it’s a process that takes too long and is open to some interpretation. On top of that, the definition has shifted over the years, with some diagnoses, like Asperger’s, disappearing altogether after being absorbed into a broader autism diagnosis. The update in the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) prompted an outcry from some parents and professionals who believed it should still be a separate category. There are also those that argue autism shouldn’t even be in the manual in the first place, since it is a development disorder, not a mental illness.
Sussing out what causes autism is crucial for diagnosis and early intervention, and would also help distinguish autism from other conditions it overlaps with.
The good news is, these newly-discovered genes bring us closer to identifying those causes.
Led by a research team comprised of Jack Kosmicki, PhD candidate at Harvard University, and Mark J. Daly, PhD, chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital, researchers combed 37,269 genetic samples from around the world. The results were presented at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, CA, on October 17, 2018.
When looking at those thousands of genes, scientists focused on exomes, the protein-coding parts of the genome. Data was collected from several groups, including over 6,000 families who had at least one child with autism but parents without it; a grouping of an additional 5,556 people with autism; and another grouping of almost 9,000 people who served as controls.
The study not only discovered new mutations, but teased apart differences in genetics between those with autism and control groups. Some of the genes have a stronger connection to intellectual disability than autism, and vice versa, and that distinction is meaningful. 47 of the 102 genes discovered have a “clear line” to intellectual disability, while 52 have closer ties to autism, and 3 have close ties to both.
“The message that autism and developmental delay, despite their overlap, have distinction is getting stronger and stronger and stronger. For autism, this is the best possible news,” said Stephan Sanders, an assistant professor of psychiatry at the University of California, San Francisco, and a researcher on the study.
A lot of the genetic mutations only affect a single amino acid, and are more likely to alter the protein’s function rather than completely disable it. Because these types of mutations are uncommon, it’s hard to parse them out in small studies. That’s why big studies like this are so important.
Other studies have been done on genes linked to autism, but not to this scale. This study gathered twice as many samples, used improved methods of analysis, and compared new data points with older data from other studies. Just three years ago, there were 65 genes associated with autism. Now that number has climbed to 102.
The results are preliminary at this point. There’s the possibility that some study participants have autism in addition to an intellectual disability and have simply never been tested for autism.
However, postdoctoral fellow Kaitlin Samocha, who presented the findings at the ASHG meeting, emphasized that the results are still promising. “This is hundreds of [new] diagnoses that we will be potentially returning to families,” she stated.