CMU, Pitt researchers help identify genes that contribute to autism

Small variations in as many as 1,000 human genes could contribute to the risk of autism, a dramatic discovery that Pittsburgh scholars say should influence detection and treatment methods during the next 20 years.

“If we can understand which genes work together to cause autism, it's the first step in finding some kind of therapy,” said Kathryn Roeder, a Carnegie Mellon University professor who helped lead an international team of researchers for two years.

Their findings released Wednesday in the prominent journal Nature mark the biggest study of its kind, relying on 14,000 genetic samples collected from autistic children, their parents and other people during the past 15 years.

The team used the data to count at least 33 genes that have definitive links to autism, a developmental disorder found in one in 68 children in the United States. That's up from nine genes identified in earlier studies.

“Not all autism genes are created equal. We're getting deeper and deeper into a list of genes that seem to have played some role in a risk for autism,” said Bernie Devlin, a University of Pittsburgh professor and Autism Sequencing Consortium member who collaborated with Roeder and contributors at several universities.

He estimated the research cost would reach at least $10 million, a tab paid in large part by the National Institutes of Health, the National Institute of Mental Health and the New York-based Simons Foundation.

Roeder, Devlin and a cross-section of students and other faculty members crafted statistical tools to let fellow researchers dig into inherited and spontaneous genetic wrinkles.

They found big increases in autism risk appear linked to rare variations in 107 genes. The finding fueled their prediction that differences in up to 1,000 genes could heighten odds of the disorder, for which there is no cure or standard medical treatment.

Researchers said they can pair the discoveries with similar recent studies and fast-advancing technology to craft sharper investigations of how subtle genetic nuances might combine with environmental factors to cause autism. A separate Pitt study suggests a connection between autism and exposure to certain airborne pollutants, but the findings presented at a conference last week were not published or peer-reviewed.

“We talk about how it takes a village to raise a child. It's going to take an army — and several of them — to pull together all the blood samples and diagnostic information to find the 1,000 needles in the haystack. But it's doable,” said Dr. Nancy Minshew, a Pitt neurology professor and autism researcher who contributed data used in the study. “That's what makes this very exciting.”

For more than 20 percent of autism cases, Minshew said, geneticists can identify a gene that probably caused the disorder.

As that figure grows, medical scholars should begin to spot different forms of autism and develop personalized treatments for each patient's genetic makeup, said Dan Smith, senior director for discovery neuroscience at the New York-based Autism Speaks advocacy group.

He said tailored treatments could be available for some cases within several years, although Minshew said not everyone with autism might want a different life.

“If we can understand that some people have a specific biological cause and other people have different biological causes, we can understand the differences in autism,” Smith said. “We think the future of having safe and effective treatments is to have them customized to an individual's personal biology.”

Researchers in Pittsburgh agreed environmental and genetic factors could have dual roles in contributing to autism. Reported incidence rates have roughly doubled in the United States since 2002, according to the Centers for Disease Control and Prevention.

Roeder said earlier research shows about 60 percent of autism is tied to genetics.

“That leaves plenty of room for environmental effects and genes and the environment interacting,” she said.

Adam Smeltz is a Trib Total Media staff writer. Reach him at 412-380-5676 or asmeltz@tribweb.com.