Carnegie Mellon University
April 04, 2012

Press Release: Carnegie Mellon and Pitt Research Provides Insight Into Genetic Makeup of Autism Spectrum Disorders

Contact: Shilo Rea / 412-268-6094 /
Anita Srikameswaran / University of Pittsburgh Schools of the Health Sciences / 412-578-9193 /

PITTSBURGH—Although it is well accepted that genetics play a strong role in autism spectrum disorders, most of the underlying causes have been a mystery — until now.

Researchers, including Carnegie Mellon University's Kathryn Roeder and the University of Pittsburgh's Bernie Devlin, have for the first time identified three genes that affect a child's risk for autism. Published in Nature, the series of studies suggests that autism spectrum disorders are caused by variations in multiple unrelated locations within the genome. These findings provide a basis for future gene discovery, diagnostics and therapeutics.

"Prior to the advent of new DNA sequencing technology, we were largely wandering around in the dark, lucky to pick up one autism gene at a time," said Matthew State, lead author of one of the studies and the Donald J. Cohen Professor of Child Psychiatry, Psychiatry and Genetics at Yale University. "Now we are getting a much better sense of what the genetic landscape looks like and have the tools in hand to find many more autism genes as we continue these experiments."

In the first study, sequencing all of the genes of families with healthy parents, who have one child affected with autism and another not, shows that de novo protein altering mutations — spontaneous mutations at conception — contribute to risk in nearly 15 percent of autism cases. These results complement previous findings that large-scale de novo deletions and duplications also are major contributors to the causes of autism.

The study also revealed that the de novo mutations were more frequent in children born to older fathers, offering at least a partial explanation for the increased risk for autism seen in children of older parents.

Yet not all de novo mutations affect risk. Results from a second study found that most newly arisen mutations seen in autism patients have no impact on risk. Most people likely carry a de novo mutation somewhere in their genes, a striking result seen across the studies. When new mutations do confer risk, they don't pile up in a few genes, showing that there are hundreds of autism genes scattered across the human genome.

Roeder, professor of statistics and computational biology at CMU, and Devlin, associate professor at the University of Pittsburgh's Departments of Psychiatry and Human Genetics, worked on the statistical analysis of the gene sequencing.

"A major implication of identifying the de novo mutations is that it provides a clear path forward for genetics research into the underpinning of autism," Roeder said. "From a statistical perspective, these kinds of data give us a roadmap for developing analytical methods for even deeper inference, including further investigating functionally-related genes together with the de novo sequence to redefine the neurobiology of autism."

Devlin added, "For example, there is a 500,000 base-pair region on chromosome 16 that is susceptible to deletions and duplications, and these events affect risk for autism. About 1 percent of all individuals diagnosed with autism carry deletions or duplications of this region in their genomes, perhaps twentyfold higher than the general populations. The region contains over 20 known genes, and which ones — if any — affect risk for autism is unknown. We are developing statistical methods to use de novo events falling in those regions to identify even more autism risk genes."

The Simons Foundation, and National Institute of Mental Health and the National Human Genome Research Institute funded this research.