A “landmark study” has identified 102 genes associated with autism spectrum disorder (ASD) in what researchers say may not only lend to understanding the causes and mechanisms behind the condition but may one day pave the way to developing precision treatments for those affected.
An international cohort of researchers from more than 50 research facilities around the world conducted the genetic sequencing study to identify associated genes as part of the Autism Sequencing Consortium (ASC), publishing their findings in Cell. In what is the largest autism sequencing study to date, scientists collected and analyzed more than 35,000 genetic samples, including nearly 12,000 from those with severe forms of ASD, looking for both inherited genetic mutations and those that may occur spontaneously when the egg or sperm is formed, or de novo mutations.
“The take-home message is that there are probably many different paths to autism,” Joseph Buxbaum, Director of the Seaver Autism Center for Research and Treatment at Mount Sinai, told IFLScience. “That is the nature of complex disorders – many of the things that have been studied now and patient-based research is complicated now because the easy stuff has been figured out.”
With more than 20,000 genes in the human genome, Buxbaum says that it is not just one major class of cells that are involved in autism but rather a variety of many disruptions in brain development and neuronal function.
“As we look more and more into autism, we are discovering that it is much more complex than we thought,” he said. “The first ‘shock’ was that it was going to be a large number of genes that could be indicators for autism, somewhere between 500 and 1,000 is our estimate.”
Genes break down into two main classes, the first being a “critically important” component of turning genes “on and off” and the other being involved in nerve function. When mutated, certain genes may alter nerve function, which can be linked to autism.
“We’re finding that about half of the genes that we discover are involved in regulating gene expression, and that is both temporal and spatial. As you develop, different genes have to be turned on and off and as each cell develops in different parts of the brain,” explained Buxbaum, adding that there is not one process in the brain that causes autism but rather a likely combination of the two.
Of the 102 genes found to be associated with ASD, 49 are also associated with other developmental delays. Genes associated with ASD and other intellectual disabilities and developmental delays often overlap, but this work begins to tease apart the specificity. The findings help to inform what brain changes underlie ASD and present a beginning for understanding new treatment approaches. Researchers hope to next test new methodologies to understanding whether specific genes are linked with ASD and if so, how. Someday, the work may lead to precision treatment whereby specific genes are targeted, manipulated, and changed in order to determine whether and what characteristics of ASD change.