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Five new genes linked to Parkinson's disease

23 November 2009
Appeared in BioNews 535
New investigations into the genetics of Parkinson's disease have identified five new genes associated with the sporadic form of the disease. The worldwide collaborative effort, published in Nature Genetics last week, gives new insight into the progression of the devastating disease that affects so many people.

Parkinson's disease is a neurodegenerative disorder that affects neurons in the part of the brain that controls movement, and is characterised by tremors and muscle stiffness. The risk of developing the disease increases with age, affecting one in 500 people in the UK. There are currently no treatments for the disease, only medicines that may help ease the symptoms. In previous studies, certain genetic risk factors have been linked to the rare inherited form of the disease, but little is known about the more common sporadic form of the disease, which is caused by multiple genetic and environmental factors.

The current findings were the results of the largest ever genome-wide association study; a study that looks for changes associated with a particular disease, in this case Parkinson's, in the whole genome of participants. Teams of collaborating scientists in the US and Europe were led by Dr Andrew Singleton, chief of the neurogenetics laboratory at the US National Institutes on Ageing, part of the National Institutes of Health, and Dr Thomas Gasser of the Hertie Institute for Clinical Brain Research, University of Tubingen, Germany. They pooled DNA samples from people of European descent to compare about 5,000 people with the Parkinson's to about 8,000 people without the disease. This study confirmed that variants in the alpha-synuclein (SNCA) and microtubule associated protein tau (MAPT) genes are linked to the sporadic disorder, which were already linked to the inherited form of the disease.

The results were then compared to those of a Japanese team led by Dr Tatsishi Toda of Kobe University, who looked at DNA samples from Japanese people to compare about 3,000 people with Parkinson's to about 18,000 healthy people. They identified new susceptibility gene variants in the subsequently named PARK16 and BST1 genes. They also confirmed the strong association for the disease for the variants in SNCA and LRRK2 genes, the latter of which had previously been identified by the US and European teams, but not the MAPT gene.

The results not only shed more light on the genetic factors involved in Parkinson's disease, but also suggest population-specific genetic susceptibility factors. Variants of PARK16, SNCA and LRRK2 genes were associated with increased risk of Parkinson's in both groups of people, whereas variants of the BST1 and MAPT genes were associated with risk of Parkinson's in only Japanese and European ancestral populations, respectively.

Singleton said in a statement: '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. We hope this new understanding will one day provide us with strategies to delay or even prevent the development of Parkinson's disease'.

Dr Richard Hodes, director of the institute, said that the findings support the notion that the sporadic and rare familial forms of the disease are related and that common genetic variability plays a role in developing the disorder'.

SOURCES & REFERENCES
Five genes linked to Parkinson's
Press Association |  16 November 2009
Genetic risk underlying Parkinson's disease
phg foundation |  19 November 2009
Mutant Genes Linked to Parkinson's in Some: Study
ABC News |  15 November 2009
Researchers Identify Gene Mutations Underlying Risk for Most Common Form of Parkinson's Disease
NIH press release |  16 November 2009
Research Sheds Light on Causes of Parkinson's
US News |  15 November 2009
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