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NIH Research Matters

May 4, 2009

Autism Tied to Genes That Influence Brain Cell Connections

Three genome-wide association studies have identified genetic factors that affect the risk of autism spectrum disorders (ASD). Understanding how these genetic variations affect brain development will suggest new strategies for diagnosing and treating ASD.

Photo of a little boy.

ASDs are characterized by social and communication problems. The disorders, which range from mild to severe, collectively affect about 1 in 150 American children.

Previous studies have found a strong genetic contribution to ASD. Yet few specific genetic risk factors had been identified, and most turned out to be rare, with unclear significance for ASD in the general population.

Genome-wide association studies involve scanning genomes — entire sets of DNA — to find small differences between people who have a disorder and people who don't. The largest of the 3 new NIH-funded studies into ASD involved more than 10,000 people, including those with ASD, their family members and other volunteers from across the United States. The study was led by Dr. Hakon Hakonarson of the University of the Pennsylvania School of Medicine and the Children's Hospital of Philadelphia.

The team reported in Nature on April 28, 2009, that several genetic variants were associated with ASD, all pointing to a spot between 2 genes, called CDH9 and CDH10, on chromosome 5. Both genes encode cadherins — cell-surface proteins that help cells adhere to each other. The researchers found that a group of about 30 genes that encode cell adhesion proteins (including cadherins) were more strongly associated with ASD than all other genes in their data set. In the developing brain, cell adhesion proteins enable neurons to migrate to the correct places and connect with other neurons.

In the second study, published in the Annals of Human Genetics, a team led by Dr. Margaret Pericak-Vance at the University of Miami Miller School of Medicine also found that ASD is associated with genetic variation near CDH9 and CDH10.

In a third study, also appearing in Nature, Hakonarson and Dr. Gerard D. Schellenberg of the University of Pennsylvania School of Medicine led a search for genes that were duplicated or deleted in people with ASD. The researchers found that many of these rare genetic glitches, known as copy number variations, affect genes involved in cell adhesion. Other variations involved genes in the ubiquitin-proteasome system, a cellular waste disposal system. The researchers suggest this system may influence ASD by altering the turnover of adhesion proteins at the cell surface.

"In most cases, it's likely that each gene contributes a small amount of risk, and interacts with other genes and environmental factors to trigger the onset of disease," Dr. Hakonarson says. He and his colleagues are now planning a more extensive genome-wide association study to gain a more complete picture of the genes and genetic interactions involved in ASD.

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Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.

NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

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This page last reviewed on December 4, 2012

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