Research 'solidifies' autism, genetic link

New research adds weight to a growing body of evidence that autism is caused by scores of rare genetic mutations, most of which occur spontaneously at conception and aren't passed from parent to child.

Researchers led by genetics professor Michael Wigler at Cold Spring Harbor Laboratory examined DNA from 1,000 families gathered by the Simons Foundation, headed by Marilyn and James Simons, founder of Renaissance Technologies in East Setauket.

The selected families have one child who is autistic but parents and siblings who are not.

"This solidifies that autism is a genetic disease. This suggests that the environment plays a limited role, but that needs to be researched in more depth," said Michael Ronemus, a researcher from Cold Spring Harbor Laboratory and an author of two papers published Thursday in the journal Neuron.

In a third, separate study published Thursday in Neuron, researchers from Yale University also found hundreds of potential genetic variations associated with autism.

Andy Shih, vice president of scientific affairs for the advocacy group Autism Speaks, said the studies don't "eliminate the role of the environment at all."

Even the possible role of vaccines in triggering autism -- a controversial theory -- cannot be dismissed based on the new studies, he said. It's possible, he added, that people with certain genetic mutations are more susceptible to vaccines.

The studies build on previous research. Wigler has proposed in the past that inherited cases of autism account for about a quarter of all cases; more than half, he and his colleagues have proposed, are the result of spontaneous mutations. How the rest of the cases are derived is unclear, Ronemus said.

The latest research supports that theory -- and points to at least 100 sites on the human genome where mutations have occurred in the autistic child. Most seem to be involved in the formation of synapses, the junctions between nerve cells, Ronemus said.

Most of the more than 200 mutations studied are also rare, meaning it could be difficult to come up with widespread treatments. "The causes of autism when fully fleshed out are likely to be very diverse, some of which may be treatable much more readily than others," Wigler said.

The findings also give some insight into why males are diagnosed with autism four times more often than females.

If most cases of autism are caused by spontaneous genetic mutations, the mutations should show up in females as often as in males. But when autism occurs in girls, the mutations "tend to be large, devastating events," which leads to more profound autism, Ronemus said. "When a smaller event occurs, it does not lead to autism."

Wigler and his colleagues suggest that females may be "resistant" to developing autism symptoms because of differences in how female and male brains develop.

Autism describes a spectrum of disorders that affect the brain's normal development of social and communication skills. About one in every 110 children in the United States is diagnosed with autism, according to Autism Speaks.

Gerald D. Fischbach, director of the Simons Foundation Autistic Research Initiative, said the DNA from 2,800 families has been collected. Because of advances in technology, he predicted that within two years "we're going to understand the genetics of autism much more completely."

Correction: A previous version of this story gave an incorrect first name for Michael Wigler.