Changes in 2 genes known to contain mutations causing rare familial forms of Parkinson's disease have been linked with the more common, sporadic form of the disease.

Parkinson's disease is a progressive neurologic disorder caused by the degeneration of nerve cells in the portion of the brain that controls movement. It affects about 1.5 million Americans. The likelihood of developing the disorder increases with age and involves a combination of environmental and genetic risk factors.

To better understand the genetic contributors, an international research team embarked upon the largest genome-wide association study of Parkinson's disease reported to date. Genome-wide association studies analyze large amounts of DNA to identify subtle genetic variations that contribute to disease.

The researchers first analyzed DNA samples of over 1,700 Europeans with Parkinson's disease and about 4,000 without it. In the November 15, 2009, online issue of Nature Genetics, the scientists reported that mutations in the alpha-synuclein (SNCA) gene and microtubule associated protein tau (MAPT) are risk factors for sporadic Parkinson's disease. These initial findings were replicated in a similar group of over 3,300 people with Parkinson's disease and over 4,500 without it.

The researchers exchanged data with colleagues performing a similar study of Japanese people. This second group also found a strong association for SNCA, but not for MAPT. They uncovered evidence for 2 additional risk variants that were then confirmed in the European study. The first, named Park16, was strongest in the Japanese population. The second variant is close to the gene LRRK2, which Singleton and Gasser's groups had previously linked to an inherited form of Parkinson's disease.

These findings support the idea that the sporadic and rare familial forms of Parkinson's disease are related. "With this better understanding of the underlying genetic variants involved in the progress of this disorder, we have more insight into the causes and underlying biology of this disease," says Singleton. "We hope this new understanding will one day provide us with strategies to delay, or even prevent, the development of Parkinson's disease."

"Future genome-wide association studies involving greater numbers of DNA samples will likely reveal additional common genetic risk factors. As we continue to use these and other novel approaches to understand complex diseases, we move closer to a complete understanding of the genetic basis of Parkinson's disease," says NIA Director Dr. Richard J. Hodes.

Related Links:
Parkinson's Disease:
http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htm
Learning About Parkinson's Disease:
http://www.genome.gov/page.cfm?pageID=10001217

November 23, 2009

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