Gene Interaction Linked to Autism Risk

Aug. 3, 2005 -- It has long been believed that complex genetic interactions are at play in autism, and new research offers some of the first concrete evidence that this is the case.

For the first time, researchers have identified an interaction between two specific genes that increases the risk that a child will develop autism. Both of the genes are associated with a chemical in the brain that has been a target of autism research for the past decade.

"This is exciting because it tells us that researchers seem to be on the right path and that we may be starting to understand the brain pathology (of autism)," says Andy Shih, PhD, who is chief science officer for the National Alliance for Autism Research, which helped fund the new study.

Autism is characterized by communication problems, social impairment, and unusual or repetitive behaviors.

Genes and Environment

It is widely thought that autism risk is determined by a combination of unidentified genetic and environmental factors. Children born into families with one autistic child are known to be at greater risk of developing autism, but the extent of that risk is not well understood.

Autism researcher Margaret Pericak-Vance, PhD and colleagues with Duke's Center for Human Genetics have long studied a brain chemical associated with slowing or stopping nerve activity, known as GABA. The GABA system acts as something of an information filter to prevent the nerves from becoming overstimulated.

It has long been suspected that this filtering process is compromised in many autistic children. Impairment of the GABA system could overwhelm the brain with sensory information, leading to many of the behavior traits associated with autism.

GABA is believed to play a key role in the early development of the brain, and the Duke researchers and others have previously shown a connection between GABA and autism.

In their latest study, Pericak-Vance and colleagues examined 14 genes that help make parts of the GABA receptor. The receptors allow the chemical to affect nerve function.

The participants in the study were 470 Caucasian families with at least one autistic member; 266 families had more than one member with autism.

The findings are reported in the September issue of the American Journal of Human Genetics, published online today.

The researchers identified one gene called GABRA4 as being associated with autism risk. Interaction with a second gene known as GABRB1 appeared to drive this risk.

"This is the first interaction of this sort that we can point to as having a real statistical correlation with autism," researcher John R. Gilbert, PhD, tells WebMD. "This is a first step, but we don't yet know where it will take us."

Better Tests and Treatments?

Gilbert says the Duke research team will now study other GABA receptors as well as other genes associated with GABA metabolism.

While much of the research has focused on the GABA system, it is clear that other genes are also involved. The thinking among the experts is that as few as 10 separate genes and as many as 100 may play a role in autism.

"Even if we prove that portions of the GABA pathway are actively involved, it will only be a factor for a minority of kids with autism," Gilbert says.

All agree, however, that the newly reported findings could advance the search for earlier diagnostic tests and autism treatments.

A number of existing medications already target the GABA system, including some antiepileptic drugs.

"As we begin to understand the GABA system as it relates to the neurological underpinnings of autism, we may advance toward new therapies," says Michael Cuccaro, PhD, who is another study researcher.

One hope, says Andy Shih, is that the research will lead to medications that can lessen or prevent many of the symptoms of autism in a subgroup of people with the disorder.

"We should consider this to be a foot in the door," he says.