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posted: 3/4/2013 6:07 AM

Study finds role of genetics in autism

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By Mark Roth
Pittsburgh Post-Gazette

In families that have children with autism, nearly half the risk of getting the brain disorder comes from inheriting an accumulation of common genetic variations from the parents, a new study shows.

The research, published in the journal Molecular Autism, showed that in families with only one child with autism, about 40 percent of the risk for the disorder is inherited. In families with two or more children with autism, about 60 percent of the risk is inherited.

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The study involved analyzing genetic variations known as single nucleotide polymorphisms in thousands of families that had donated genetic material to the Simons Simplex Collection, where only one child has the disorder, or the Autism Genome Project, where two or more children in a family have it.

For those who would like a simple, clear explanation for the seemingly alarming increase in autism in America, the finding that hundreds of common genetic variations may incrementally contribute to the condition may be frustrating.

"I can understand the frustration," said Bernard Devlin, a psychiatry professor at the University of Pittsburgh and the main author of the multi-institution study. "It would be nice to have a simple explanation, and in fact, it's a cause for concern in the research community, because one way to view it is that autism and other psychiatric disorders are so complex they will be intractable for any kind of drug therapy.

"At the same time," he said, "there is another point of view -- that while there are a large number of genes involved, they do seem to be converging on a few brain systems," so that drugs that target those parts of the brain may one day be effective.

For example, he noted, scientists know there are hundreds of genes that contribute to high blood pressure. Despite that, they have found effective drugs to attack hypertension.

The purpose of the latest study was not to explore possible treatments, he noted. Instead, it was designed to measure how common genetic traits might contribute to autism, which affects an estimated 1 in 88 American children and causes impaired social communication, repetitive behaviors and obsessive interests.

To understand how autism might be partly inherited and why not all children in a family get it, Devlin used height as an analogy.

Scientists know that about 80 percent of a person's height is inherited, even though there are hundreds of genes that contribute to tallness. But almost everyone knows of a family with tall parents where at least one child is shorter than average. In those cases, he explained, the child got a different combination of genetic variants from his parents than his siblings did.

In a similar way, the child in a family who gets autism may have received as many as 500 genetic variants associated with the disorder from his parents, while his unaffected sister may have gotten far fewer.

Devlin also used the height analogy to talk about possible environmental contributions to autism. Even though height within families is mostly inherited, people throughout the world have been getting taller from generation to generation, suggesting that some environmental factors -- better diets or lack of pollution -- are making an impact.

In the same way, "environmental factors could be an important source of risk above and beyond the genetic factors" in autism. One of the leading possibilities is the father's age -- older fathers have been associated with a greater risk for autism in children. Other candidates may be synthetic analogs of hormones in plastics or air pollution, Devlin said, but no one knows for sure yet.

The study involved researchers from nearly 20 institutions in the United States and Canada. Its statistical techniques were based on groundbreaking work by Jian Yang at Queensland Institute of Medical Research in Australia.

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